9.C.15 The Animal Calmodulin-dependent E.R. Secretion Pathway (CSP) Family

Shao and Hegde (Shao and Hegde, 2011) have shown that both in vivo and in vitro, small secretory proteins can enter the ER posttranslationally via a transient cytosolic intermediate. This intermediate contained calmodulin selectively bound to the signal peptides of small secretory proteins. Calmodulin maintained the translocation competence of small-protein precursors, precluded their aggregation and degradation, and minimized their inappropriate interactions with other cytosolic polypeptide-binding proteins. Acute inhibition of calmodulin specifically impaired small-protein translocation in vitro and in cells. These findings establish a mammalian posttranslational pathway for small-protein secretion and identify an unexpected role for calmodulin in chaperoning these precursors safely through the cytosol (Shao and Hegde, 2011).It seems likely that the small secretory proteins maintained in a folding-competent configuration in the cytoplasm by calmodulin feed into the general secretory pathway (TC#3.A.5). However this needs to be established (Shao and Hegde, 2011).



Miwa, N., T. Uebi, and S. Kawamura. (2008). S100-annexin complexes--biology of conditional association. FEBS J. 275: 4945-4955.

Shao, S. and R.S. Hegde. (2011). A calmodulin-dependent translocation pathway for small secretory proteins. Cell 147: 1576-1588.


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