Astrocytes modulate neuronal development by S100A6 signaling.

ABSTRACT: Neuronal morphogenesis relies on intercellular signaling. Astrocytes release metabolites, trophic, and guidance factors to promote neuronal maturation. In contrast, the mechanisms by which astrocytes could limit and stabilize neuronal connectivity remain less explored. Here, we find cortical astrocytes to express and release S100A6, a Ca²⁺-binding protein ('calcyclin'). Simultaneously, the majority of cortical neurons expressed calcyclin-binding protein (CaCyBp), a bona fide binding partner for S100A6. In neurons, CaCyBp maintains the unfolded protein response pathway, thereby controlling proteostasis. When released, S100A6 inhibits CaCyBp-mediated signaling, thus slowing protein turnover, and, consequently, neuritogenesis. In the cerebral cortex of male mice, S100A6-CaCyBp sign

SUBMITTER: Cinquina V 

PROVIDER: S-EPMC12518605 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature