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Inositol 1,4,5-trisphosphate receptor type1 (IP3R1) plays an important role in neuronal functions; however, the lateral diffusion of IP3R1 on the endoplasmic reticulum membrane and its regulation in the living neurons remain unknown. We expressed green fluorescent protein-tagged IP3R1 in cultured rat hippocampal neurons and observed the lateral diffusion by the fluorescence recovery after photobleaching technique. IP3R1 showed lateral diffusion with an effective diffusion constant of ∼0.3 μm2/s. Depletion of actin filaments increased the diffusion constant of IP3R1, suggesting that the diffusion of IP3R1 is regulated negatively through actin filaments. We also found that protein 4.1N, which binds to IP3R1 and contains an actin-spectrin-binding region, was responsible for this actin regulation of the IP3R1 diffusion constant. Overexpression of dominant-negative 4.1N and blockade of 4.1N binding to IP3R1 increased the IP3R1 diffusion constant. The diffusion of IP3R type 3 (IP3R3), one of the isoforms of IP3Rs lacking the binding ability to 4.1N, was not dependent on actin filaments but became dependent on actin filaments after the addition of a 4.1N-binding sequence. These data suggest that 4.1N serves as a linker protein between IP3R1 and actin filaments. This actin filament-dependent regulation of IP3R1 diffusion may be important for the spatiotemporal regulation of intracellular Ca2+ signaling. Inositol 1,4,5-trisphosphate receptor type1 (IP3R1) plays an important role in neuronal functions; however, the lateral diffusion of IP3R1 on the endoplasmic reticulum membrane and its regulation in the living neurons remain unknown. We expressed green fluorescent protein-tagged IP3R1 in cultured rat hippocampal neurons and observed the lateral diffusion by the fluorescence recovery after photobleaching technique. IP3R1 showed lateral diffusion with an effective diffusion constant of ∼0.3 μm2/s. Depletion of actin filaments increased the diffusion constant of IP3R1, suggesting that the diffusion of IP3R1 is regulated negatively through actin filaments. We also found that protein 4.1N, which binds to IP3R1 and contains an actin-spectrin-binding region, was responsible for this actin regulation of the IP3R1 diffusion constant. Overexpression of dominant-negative 4.1N and blockade of 4.1N binding to IP3R1 increased the IP3R1 diffusion constant. The diffusion of IP3R type 3 (IP3R3), one of the isoforms of IP3Rs lacking the binding ability to 4.1N, was not dependent on actin filaments but became dependent on actin filaments after the addition of a 4.1N-binding sequence. These data suggest that 4.1N serves as a linker protein between IP3R1 and actin filaments. This actin filament-dependent regulation of IP3R1 diffusion may be important for the spatiotemporal regulation of intracellular Ca2+ signaling. Inositol 1,4,5-trisphosphate (IP3) 1The abbreviations used are: IP3, inositol 1,4,5-trisphosphate; IP3R, inositol 1,4,5-trisphosphate receptor; ER, endoplasmic reticulum; IICR, IP -induced Ca2+ release; IP3R1, inositol 1,4,5-trisphosphate receptor type 1; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid; AMPAR, AMPA type glutamate receptor; FRAP, fluorescence recovery after photobleaching; SERCA, sarcoplasmic/endoplasmic reticulum calcium-ATPase; IP3R3, inositol 1,4,5-trisphosphate receptor type 3; GFP, green fluorescent protein; mRFP, monomeric red fluorescent protein; CTD, C-terminal domain; CTT, C-terminal cytoplasmic tail; HA, hemagglutinin. receptors (IP3Rs) are intracellular Ca2+ channels that are responsible for Ca2+ release from intracellular stores (1Berridge M.J. Nature. 1993; 361: 315-325Crossref PubMed Scopus (6188) Google Scholar) and located on the membrane of the endoplasmic reticulum (ER). IP3, which is generated in response to various extracellular stimuli, binds to IP3Rs and induces Ca2+ release (IP3-induced Ca2+ release; IICR) (1Berridge M.J. Nature. 1993; 361: 315-325Crossref PubMed Scopus (6188) Google Scholar, 2Furuichi T. Mikoshiba K. J. Neurochem. 1995; 64: 953-960Crossref PubMed Scopus (181) Google Scholar). IICR plays crucial roles in various neuronal activities. For example, mouse strains mutated in the IP3R type 1 (IP3R1) gene display severe ataxia and epileptic seizures (3Matsumoto M. Nakagawa T. Inoue T. Nagata E. Tanaka K. Takano H. Minowa O. Kuno J. Sakakibara S. Yamada M. Yoneshima H. Miyawaki A. Fukuuchi Y. Furuichi T. Okano H. Mikoshiba K. Noda T. Nature. 1996; 379: 168-171Crossref PubMed Scopus (372) Google Scholar, 4Street V.A. Bosma M.M. Demas V.P. Regan M.R. Lin D.D. Robinson L.C. Agnew W.S. Tempel B.L. J. Neurosci. 1997; 17: 635-645Crossref PubMed Google Scholar). The control of nerve growth in chick dorsal root ganglia neurons is dependent on IP3R1 (5Takei K. Shin R.M. Inoue T. Kato K. Mikoshiba K. Science. 1998; 282: 1705-1708Crossref PubMed Scopus (161) Google Scholar). IICR is also known to be involved in long term potentiation and long term depression in the hippocampal CA1 area (6Fujii S. Matsumoto M. Igarashi K. Kato H. Mikoshiba K. Learn. Mem. 2000; 7: 312-320Crossref PubMed Scopus (105) Google Scholar, 7Nishiyama M. Hong K. Mikoshiba K. Poo M.M. Kato K. Nature. 2000; 408: 584-588Crossref PubMed Scopus (507) Google Scholar) and in long term depression in cerebellar Purkinje cells (8Inoue T. Kato K. Kohda K. Mikoshiba K. J. Neurosci. 1998; 18: 5366-5373Crossref PubMed Google Scholar). Interestingly, IICR in neurons is highly restricted spatially (9Finch E.A. Augustine G.J. Nature. 1998; 396: 753-756Crossref PubMed Scopus (452) Google Scholar, 10Takechi H. Eilers J. Konnerth A. Nature. 1998; 396: 757-760Crossref PubMed Scopus (353) Google Scholar), although the ER is spread throughout the cell, and the induction of synaptic plasticity (11Miyata M. Finch E.A. Khiroug L. Hashimoto K. Hayasaka S. Oda S.I. Inouye M. Takagishi Y. Augustine G.J. Kano M. Neuron. 2000; 28: 233-244Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar) and regulation of nerve growth (5Takei K. Shin R.M. Inoue T. Kato K. Mikoshiba K. Science. 1998; 282: 1705-1708Crossref PubMed Scopus (161) Google Scholar) require spatially restricted IICR. Some ER Ca2+-handling proteins including IP3Rs show uneven distribution patterns (12Papp S. Dziak E. Michalak M. Opas M. J. Cell Biol. 2003; 160: 475-479Crossref PubMed Scopus (79) Google Scholar), and this heterogeneity is postulated to be responsible for the spatially and temporally heterogeneous Ca2+ signaling patterns. Thus, targeting of IP3Rs to specific regions in the cell may be one of the important factors in the spatial regulation of IICR; however, the molecular mechanisms underlying the spatial regulation of IICR remain to be elucidated. The dynamics of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) type glutamate receptor (AMPAR) have been intensively studied. In addition to an elaborate mechanism for insertion and removal from the plasma membrane (13Carroll R.C. Beattie E.C. von Zastrow M. Malenka R.C. Nat. Rev. Neurosci. 2001; 2: 315-324Crossref PubMed Scopus (360) Google Scholar), the lateral diffusion of AMPAR on the plasma membrane is regulated actively, especially by local Ca2+ signals (14Borgdorff A.J. Choquet D. Nature. 2002; 417: 649-653Crossref PubMed Scopus (426) Google Scholar, 15Tardin C. Cognet L. Bats C. Lounis B. Choquet D. EMBO J. 2003; 22: 4656-4665Crossref PubMed Scopus (319) Google Scholar). All of the dynamics of AMPAR have been implied to play important roles in the regulation of synaptic transmission and plasticity. Thus, the distribution pattern of IP3Rs and their dynamics in dendrites is also considered to be important for the fine tuning of Ca2+-dependent events, such as synaptic plasticity, that are little understood to date. We have shown the existence of vesicular ERs that are transported along dendrites bi-directionally with a fast velocity (0.2–0.3 μm/s) (16Bannai H. Inoue T. Nakayama T. Hattori M. Mikoshiba K. J. Cell Sci. 2004; 117: 163-175Crossref PubMed Scopus (86) Google Scholar), in addition to the ER in reticular structure. In this study, we focused on the dynamics of ER membrane proteins in the reticular ER in dendrites of cultured hippocampal neurons and observed their diffusive movements using the fluorescence recovery after photobleaching (FRAP) technique. To our surprise, the diffusive movement of IP3R1 was regulated through actin filaments, and this regulation was not seen for other ER membrane proteins such as sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA) and IP3R type 3 (IP3R3). Furthermore, we found that the actin-spectrin-binding protein 4.1N, which binds to the C terminus of IP3R1 (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar), may play crucial roles in the actin-dependent regulation of IP3R1 diffusion. DNA Constructions—All of the plasmids were propagated in the Escherichia coli strain HB101. All PCR products were verified by nucleotide sequencing using an ABI PRISM 377 automated sequencer (Applied Biosystems, Foster City, CA). The constructions of GFP-tagged sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (GFP-SERCA2a) (18Aihara Y. Inoue T. Tashiro T. Okamoto K. Komiya Y. Mikoshiba K. J. Neurosci. Res. 2001; 65: 236-246Crossref PubMed Scopus (27) Google Scholar), GFP-tagged IP3R1 (GFP-IP3R1), GFP-IP3R1-ΔCTT14aa, and HA-4.1N-FL (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar) were described previously. GFP-tagged IP3R3 (GFP-IP3R3) 2M. Iwai, Y. Tateishi, M. Hattori, A. Mizutani, A. Futatsugi, T. Inoue, T. Furuichi, T. Michikawa, and K. Mikoshiba, unpublished data. was generated using cDNA clones of mouse IP3R3 and a cDNA fragment coding enhanced green fluorescent protein. GFP-H2Ldin (19Marguet D. Spiliotis E.T. Pentcheva T. Lebowitz M. Schneck J. Edidin M. Immunity. 1999; 11: 231-240Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar) was kindly provided by Dr. Edidin (The Johns Hopkins University, Baltimore, MD). DsRed2–4.1N-FL and DsRed2–4.1N-CTD were generated by replacing a Venus fragment, a variant of yellow fluorescent protein (20Nagai T. Ibata K. Park E.S. Kubota M. Mikoshiba K. Miyawaki A. Nat. Biotechnol. 2002; 20: 87-90Crossref PubMed Scopus (2197) Google Scholar), in pcDNA3-Venus-4.1N-FL and pcDNA3-Venus-4.1N-CTD (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar) with DsRed2 (BD Biosciences, San Jose, CA), a gene encoding a red fluorescent protein. A monomeric red fluorescent protein (mRFP) expression plasmid (pcDNA3.1/Zeo+-mRFP) was generated by inserting a fragment encoding mRFP (21Campbell R.E. O. Sci. S. A. 2002; PubMed Scopus Google Scholar), which was kindly provided by Dr. of San CA), the of with the C-terminal of IP3R1, was generated by inserting a DNA fragment to of mouse IP3R1 the of To a cDNA we 1 3 and cDNA encoding of IP3R1 and of IP3R3 were by PCR with 1 and and 3 and and and as The PCR products were and using and to a sequence. The and the were with and and to the in and of of hippocampal neurons were from the of as described (16Bannai H. Inoue T. Nakayama T. Hattori M. Mikoshiba K. J. Cell Sci. 2004; 117: 163-175Crossref PubMed Scopus (86) Google Scholar). cells were on a of and cultured in with and and The were with of the on in using a M. C. J. Neurosci. Res. 1999; PubMed Scopus Google Scholar). The cells were used for after the and the the was with of the cells were a to an with a The was using a that the The was and was through a The was as was the photobleaching with a of and a area and the area of the of was with with a area for The and area were to the and the fluorescence recovery the area was for The were a of The shown in 1 and and were after to the The is using 3 3 spatial the of in the is with the of its 3 3 are of is dependent on actin filaments, that of is of A and on actin of the of neurons with and the of and with and that the of is in the of the that the actin filaments A and that of is with which the of and The data the The in the of neurons The of and for are the data shown in of the a (18Aihara Y. Inoue T. Tashiro T. Okamoto K. Komiya Y. Mikoshiba K. J. Neurosci. Res. 2001; 65: 236-246Crossref PubMed Scopus (27) Google Scholar), we the movement of ER proteins as the velocity of the fluorescence recovery after which was effective for the of protein diffusion the but we not to the diffusion of other proteins in the To this we a that of the effective diffusion of ER proteins from the We a described by J. S. J. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar) in which the movement of proteins on the ER membrane is by diffusion in this study, we considered the ER in neuronal dendrites to be along the of the dendrites were the We the movement of the fluorescent signals as diffusion using the by J. S. J. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). To the data which of a and a of of to a of data the were the the cells were that the dendrites in the the the was to that the was to the A was including the of the with its long in the and was this The fluorescence data in the was in the by to data which were to a data To along the were to a of The which the of the in the of the was by the a of the that not cell The constant of the photobleaching the of the was by the fluorescence of the cell area to an We the using 1 and which are from and of J. S. J. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar) by to the is the is the is the of the and is the fluorescence to which the data was to the fluorescence distribution from the The in were used as a and for which the fluorescent of the the We with of the and the that the data All of the were using on a We have the existence of vesicular which are transported along in addition to the reticular ER in hippocampal neurons (16Bannai H. Inoue T. Nakayama T. Hattori M. Mikoshiba K. J. Cell Sci. 2004; 117: 163-175Crossref PubMed Scopus (86) Google Scholar). the fluorescence of reticular ER was that of vesicular ERs in dendrites not we that the of from the vesicular ER was in this The data were expressed as the was using CA). A between the was by an with were considered to be and of A and were in and The of and in the were 1 and To the to the a of the of the was to an of the neurons were with A and for 1 with for 3 in To that the was cells were with an CA). The cells were with in for with in for and with in the cells were with the were used as the for the and cells were in with was using to the cells were 1 after and the were as described L. J. Neurosci. 2000; 20: PubMed Google Scholar, in Scholar). The cell were for and the were used for The were with of an mouse an for 1 and with of protein for The were and with The proteins were by in for 3 and by The proteins were to and the were with an green fluorescent protein and an San CA). of GFP-tagged ER in rat hippocampal neurons were with GFP-tagged IP3R1 GFP-tagged (GFP-SERCA2a) to the dynamics of ER membrane proteins in dendrites A of was and the recovery of fluorescence the area was shown in and the area from The movements of proteins were also by from to This diffusive to the effective diffusion constant by to a diffusion which was for diffusion in a such as a To the of this in neuronal we the of a ER GFP-tagged mouse (19Marguet D. Spiliotis E.T. Pentcheva T. Lebowitz M. Schneck J. Edidin M. Immunity. 1999; 11: 231-240Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar) in dendrites and this with that for the protein in The diffusion of GFP-H2Ldin been to be in the of with the with 1 in cell (19Marguet D. Spiliotis E.T. Pentcheva T. Lebowitz M. Schneck J. Edidin M. Immunity. 1999; 11: 231-240Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar). In dendrites of hippocampal in which for with 1 is H. H. A. D. H. J. 1997; PubMed Scopus Google Scholar), the of GFP-H2Ldin was The between the that our the diffusion in Interestingly, the of was of and GFP-H2Ldin to diffusion of plasma membrane proteins is regulated by the especially actin filaments D. A. Nat. Rev. Neurosci. 2003; PubMed Scopus Google Scholar, J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). We that the diffusion of IP3R1 was by an with the and this by and actin filaments was used to and A and were used to and actin filaments, The of the with was by in cultured rat hippocampal with in neurons was not A the of actin filaments, of actin filaments and with the of and to and and that the of is an important for the diffusion of ER To our surprise, of actin filaments the diffusion of The of was increased by A and by to and the of after with A and and These data suggest that the movement of is negatively regulated through actin filaments, that of is We to on the molecular mechanisms that the diffusion of 4.1N the of found that protein 4.1N, an actin-spectrin-binding binds to the C-terminal cytoplasmic of IP3R1 its C-terminal and IP3R1 in the cell (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). 4.1N is expressed in including in the and its expression also been shown in cultured hippocampal neurons S. D. M. J. Neurosci. 1999; PubMed Google Scholar), we considered 4.1N to be a for the control of IP3R1 diffusion. To this we the of DsRed2 red fluorescent 4.1N proteins on the of Overexpression of 4.1N DsRed2 little on the of and we the of of a dominant-negative of 4.1N, a C-terminal of 4.1N that the actin-spectrin-binding (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar), on the of Interestingly, of the dominant-negative 4.1N increased the of to which was to the after A the other the of of the of DsRed2–4.1N-CTD These suggest that DsRed2–4.1N-CTD the of with 4.1N and our that actin filaments the diffusion of through diffusion of various of in a by the The 4.1N-binding of IP3R1 was as the C-terminal of the cytoplasmic (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). To the 4.1N with was responsible for the regulation of we observed the diffusion of GFP-tagged IP3R3 one of the isoforms of IP3Rs that a to We that not to 4.1N by The of was that of the other the diffusion of with its C-terminal showed to IP3R1 to We the binding of to 4.1N by The of in dendrites was to that of and that of A increased the of to which was to that of This that serves as a linker for the diffusion control of is involved in the regulation of diffusion. the of and and the of with A. that the of is that of and that is increased by A the of and with of which are that of The data the The in the of neurons The of in A and are the data shown in To was involved in the regulation of diffusion through with 4.1N, IP3R1 lacking the which not to 4.1N (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar), was expressed in The of was that of and to of and We a which is to with the for the binding in the increased the diffusion constant of the diffusion constant of and Overexpression of mRFP not the of of the we that the acid of IP3R1, is involved in the actin-dependent regulation of the diffusion by with 4.1N of the IP3R1 the study, we showed that ER membrane proteins IP3R1, and on the reticular ER membrane in neuronal dendrites 1 and This is the the diffusion of ER membrane proteins and their in neuronal The of was of and GFP-H2Ldin and This heterogeneity in the diffusion of ER been that the diffusion of proteins on is dependent on the of the of protein M. Sci. S. A. PubMed Scopus Google Scholar), although this not to be with our The of and which are to have regions of were and the of was that of the in of their regions as as of the Thus, we that the of with of other ER proteins is not to the in molecular but to a mechanism specific for IP3R1 diffusion. We that the movement velocity of the GFP-tagged C-terminal of IP3R1, the region, was to that of in the of chick dorsal root neurons (18Aihara Y. Inoue T. Tashiro T. Okamoto K. Komiya Y. Mikoshiba K. J. Neurosci. Res. 2001; 65: 236-246Crossref PubMed Scopus (27) Google Scholar). The between this and the one may from the in the the cell the of the IP3R1 used of the diffusion of plasma membrane proteins is regulated by the especially actin filaments in D. A. Nat. Rev. Neurosci. 2003; PubMed Scopus Google and J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). filaments are also involved in the regulation of diffusion in the plasma membrane T. K. H. K. A. J. Cell Biol. 2002; PubMed Scopus Google Scholar). In this study, we have an of regulation of ER protein diffusion for the been that the of actin filaments IICR Y. K. J. Neurochem. 2002; PubMed Scopus Google Scholar). The specific regulation of IP3R1 diffusion by actin filaments found in the be underlying such of Ca2+ release by actin in The of was the for the diffusion of and and are known to be involved in the dynamics of the ER such as and C. Full Text PDF PubMed Scopus Google Scholar, Full Text PDF PubMed Scopus Google Scholar), the diffusion of and may not be dependent on their with but on in the dynamics of the ER are to this and the of to the regulation of the dynamics of other ER proteins may be for this In the study, we focused on an actin filament-dependent mechanism for the diffusion of through 4.1N and a of the regulation of IP3R1 diffusion. 4.1N that contains an actin-spectrin-binding was as a binding protein of the C-terminal of IP3R1 (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). other protein play roles in the of the plasma and 4.1N is also postulated to play such a role S. D. M. J. Neurosci. 1999; PubMed Google Scholar). 4.1N is also to play roles in the cell expression of receptor In 4.1N is for IP3R1 to the membrane (17Zhang S. Mizutani A. Hisatsune C. Higo T. Bannai H. Nakayama T. Hattori M. Mikoshiba K. J. Biol. Chem. 2003; 278: 4048-4056Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). In is suggesting that 4.1N is involved in the regulation of the expression of receptors and channels in the plasma such as and Lin 2002; PubMed Scopus Google Scholar) and AMPA L. J. Neurosci. 2000; 20: PubMed Google Scholar) In the of AMPAR to actin filaments through 4.1N is postulated L. J. Neurosci. 2000; 20: PubMed Google Scholar). These with the that 4.1N may proteins on the plasma membrane and the ER membrane in the data not that 4.1N is the protein for IP3R1 diffusion. proteins are known E. Biol. 2004; PubMed Scopus Google Scholar), including proteins that with actin filaments, and L. A. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus (109) Google Scholar), proteins other 4.1N may also to the regulation of IP3R1 diffusion through to actin filaments. This is the in the mechanism of IP3R1 diffusion. we to on the roles for this mechanism of IP3R1 diffusion. IP3R1 is responsible for various neuronal synaptic plasticity in (6Fujii S. Matsumoto M. Igarashi K. Kato H. Mikoshiba K. Learn. Mem. 2000; 7: 312-320Crossref PubMed Scopus (105) Google Scholar, 7Nishiyama M. Hong K. Mikoshiba K. Poo M.M. Kato K. Nature. 2000; 408: 584-588Crossref PubMed Scopus (507) Google Scholar, T. Kato K. Kohda K. Mikoshiba K. J. Neurosci. 1998; 18: 5366-5373Crossref PubMed Google Scholar) and nerve growth in growth (5Takei K. Shin R.M. Inoue T. Kato K. Mikoshiba K. Science. 1998; 282: 1705-1708Crossref PubMed Scopus (161) Google Scholar). Interestingly, actin filaments are in the and growth IICR from IP3R1 is to be important for S. H. M. C. A. Sci. S. A. 2001; PubMed Scopus Google Scholar, J. Cell Biol. PubMed Scopus Google Scholar, L. J. Cell Biol. PubMed Scopus Google Scholar). distribution of of the Ca2+-handling ER proteins is considered to be important for spatially Ca2+ (12Papp S. Dziak E. Michalak M. Opas M. J. Cell Biol. 2003; 160: 475-479Crossref PubMed Scopus (79) Google Scholar), and regulation of IP3R1 diffusion by actin filaments may be involved in the spatial heterogeneity of IP3R1, the spatial regulation of Ca2+ release that various neuronal such as synaptic plasticity and nerve especially in neurons We are to Dr. for the of mRFP and to Dr. M. Edidin for the of We Dr. M. Hattori and Dr. T. for and M. Iwai, Y. Tateishi, Dr. A. Mizutani, and for
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