Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies

Figure 1. Schematic representation of human CaV2.1 mutations causing episodic ataxia type 2 (EA2). Please note that residue numbering varies between studies due to the existence of multiple CACNA1A splice variants; residue numbers indicated reflect those stated in the original report. Citations to the indicated mutations are listed as follows: E147K—Imbrici et al., 2004; G162V—Maksemous et al. (2016); R192W—Soden et al. (2014); R198Q—Indelicato et al. (2019); Y248C—Zafeiriou et al. (2009); Y248N—Choi et al. (2017); H253Y—van den Maagdenberg et al. (2002); C256R—Mantuano et al. (2004); R279C—Maksemous et al. (2016); C287Y—Jen et al. (2004); G293R—Yue et al. (1997); G297R—Tantsis et al. (2016); D302N—Maksemous et al. (2016); R387G—Maksemous et al. (2016); E388K—Nikaido et al. (2011); L389F—Mantuano et al. (2010); G411W—Maksemous et al. (2016); A454T—Cricchi et al. (2007); R455Q—Isaacs et al. (2017); T501M—Mantuano et al. (2010); G533K—Scoggan et al. (2006); G540R—Rajakulendran et al. (2010a); L621R—Rajakulendran et al. (2010a); G638D—Cuenca-León et al. (2009); I712V—Guerin et al. (2008); M798T—Mantuano et al. (2010); P897R—Mantuano et al. (2010); F1404C—Jen et al. (2001); R1433Q—Pietrobon…

Figure 2. Schematic representation of human CaV2.1 mutations causing familial hemiplegic migraine type 1 (FHM1). Please note that residue numbering varies between studies due to the existence of multiple CACNA1A splice variants; residue numbers indicated reflect those stated in the original report. Citations to the indicated mutations are listed as follows: R192Q—Ophoff et al. (1996); R195K—Ducros et al. (2001); S218L—Kors et al. (2001); P225H—Stuart et al. (2012); G230V—Yang et al. (2014); F363S—Riant et al. (2010); V581M—Cuenca-León et al. (2008); V581L—Freilinger et al. (2011); R583Q—Battistini et al. (1999); T666M—Ophoff et al. (1996); V714A—Ophoff et al. (1996); D715E—Ducros et al. (2001); E1015K—Grieco et al. (2018); Y1245C—Cuenca-León et al. (2008); K1336E—Ducros et al. (2001); R1347Q—Alonso et al. (2004); C1370Y—Thomsen et al. (2007); Y1385C—Vahedi et al. (2000); V1457L—Carrera et al. (1999); F1506S—Riant et al. (2010); F1506Y—Pelzer et al. (2018); I1512T—Grieco et al. (2018); C1535S—Dichgans et al. (2005); F1609L—Pelzer et al. (2018); R1668W—Ducros et al. (2001); K1670R—Riant et al. (2010); L1682P—Weiss et al. (2007); W1684R—Ducros et al. (2001); V1696I—Ducros et al. (2001);…

Figure 3. Missense CaV2.1 mutations leading to neurodevelopmental disorders. The zebrafish fakir and tb204a mutants are also depicted as yellow circles. Red circles indicate a loss-of-function human mutation. Blue circles indicate a gain-of-function human mutation. Magenta circles indicate a yet-to-be functionally characterized human mutation. Specific references are indicated below. As in Figures 1, 2, please note that residue numbering varies between studies due to: (1) the existence of multiple known CACNA1A splice variants; and (2) species differences between humans and zebrafish. The CaV2.1 schematic was modified from Tyagi et al. (2019) with permission of the authors. These mutations are discussed in sections “The Expanding Spectrum OF CaV2.1-α1A Channelopathies” and “Zebrafish as a Model SYSTEM for the Study of Severe CaV2.1 Channelopathies.”