PKC induces release of a functional ectodomain of the guidance cue semaphorin6A

Abstract

Semaphorins (Semas) are a family of secreted and transmembrane proteins that play critical roles in development. Interestingly, several vertebrate transmembrane Sema classes are capable of producing functional soluble ectodomains. However, little is known of soluble Sema6 ectodomains in the nervous system. Herein, we show that the soluble Sema6A ectodomain, sSema6A, exhibits natural and protein kinase C (PKC)‐induced release. We show that PKC mediates Sema6A phosphorylation at specific sites and while this phosphorylation is not the primary mechanism regulating sSema6A production, we found that the intracellular domain confers resistance to ectodomain release. Finally, sSema6A is functional as it promotes the cohesion of zebrafish early eye field explants. This suggests that in addition to its canonical contact‐mediated functions, Sema6A may have regulated, long‐range, forward‐signaling capacity.

SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability

“…6a). Although SEMA6A is produced as a transmembrane protein, its extracellular domain can be released to generate a secreted ectodomain 48 . Therefore, we transfected COS-7 cells with a vector encoding mouse SEMA6A ectodomain (SEMA6A ECTO ) and used conditioned medium to stimulate ECs.…”