SPCA2 couples Ca influx via Orai1 to Cauptake into the Golgi/secretory pathway

Dysregulation of the Golgi/Secretory Pathway Catransport ATPase SPCA2 is implicated in breast cancer. During lactation and in luminal breast cancer types, SPCA2 interacts with the plasma membrane Cachannel Orai1, promoting constitutive Cainflux, which is termed store independent Caentry (SICE). The mechanism of SPCA2/Orai1 interaction depends on the N- and C-termini of SPCA2. These extensions may play a dual role in activating not only Orai1, but also Catransport into the Golgi/secretory pathway, which we tested by investigating the impact of various SPCA2 N- and/or C-terminal truncations on SICE and Catransport activity of SPCA2. C-terminal truncations impair SICE and SPCA2 activity, but also affect targeting, whereas N-terminal truncations affect targeting and inactivate SPCA2, but remarkably, SICE activation remains unaffected. Importantly, overexpression of SPCA2 increases the Cacontent of non-ER stores, which depends on Orai1 and SPCA2 activity. Thus, Orai1-mediated Ca-influx and SPCA2-mediated Cauptake activity into the Golgi/secretory pathway might be coupled possibly in a microdomain. This channel/pump complex may efficiently transfer Cainto the secretory pathway, which might play a role in SPCA2-expressing secretory cells, such as mammary gland during lactation.

Publication year:2017

BOF-keylabel:yes

IOF-keylabel:yes

BOF-publication weight:1

CSS-citation score:2

Authors from:Higher Education

Accessibility:Open