Key result
The Slo1_DEC isoform showed dramatically reduced surface expression compared to Slo1_ERL or Slo1_VYR, remaining largely localized in the endoplasmic reticulum and interacting specifically with PP2A-A.
The Slo1_DEC isoform exhibits distinct trafficking and protein interactions, including specific binding to PP2A-A that reduces its phosphorylation, highlighting isoform-specific regulatory mechanisms.
This is the authors' abstract. We don't add key points for this paper.
The pore-forming subunit of the large-conductance Ca(2+)-dependent K(+) (Slo1) channel is encoded by one gene. However, the functional properties of Slo1 channels are diverse in part because of their numerous regulatory mechanisms including posttranslational modification and alternative splicing. In particular, multiple splice variants of the pore-forming subunit have been reported but their significance is only beginning to be elucidated. Here we examined the cell biological properties of the three common C-terminal isoforms that differ in the last 8 (Slo1_ERL and Slo1_VYR) or 61 residues (Slo1_DEC). We found that Slo1_DEC, the longest isoform, shows dramatically reduced surface expression compared to that of Slo1_ERL or Slo1_VYR. Immunocytochemistry revealed that a large fraction of Slo1_DEC remains localized in endoplasmic reticulum (ER). Using a GST fusion protein containing the Slo1_DEC-specific sequence, affinity purification was carried out to isolate interacting proteins. The identified proteins include protein phosphatase 2A (PP2A-A), actin, and tubulin. The PP2A-A interaction is specific to Slo1_DEC and causes a significant reduction of phosphorylation in Slo1_DEC but not Slo1_ERL or Slo1_VYR. The results together support the notion that Slo1_DEC nucleates isoform-specific protein complexes and possesses a cis element(s) for regulating trafficking of the Slo1 channels.
Slo1 isoform trafficking differences may affect BK channel function in cardiovascular tissues; leaves open in vivo roles and clinical relevance.
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Ma et al. (2007) studied this question. Slo1_DEC isoform vs. Slo1_ERL or Slo1_VYR isoforms was evaluated on Surface expression and protein interactions. The Slo1_DEC isoform showed dramatically reduced surface expression compared to Slo1_ERL or Slo1_VYR, remaining largely localized in the endoplasmic reticulum and interacting specifically with PP2A-A.
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