The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774.

Background: Regulation of group I p21-activated kinases is based on dimeric conformation. Results: PAK3a forms regulatory heterodimers with PAK1 in vitro and in vivo. Conclusion: Heterodimerization of PAK3a and PAK1 links PAK pathways in brain. Significance: Analyzing the molecular mechanisms of PAKs regulation could help to understand the pathophysiology of some cancers and mental disabilities.

Background:The mental retardation p21-activated kinase (PAK3) protein regulates synaptic plasticity through the regulation of cytoskeleton dynamics of dendritic spines. Results: PAK3 binds the Grb4/Nck2 adaptor in brain, and inhibition of this complex alters synaptic currents but not spine morphology. Conclusion:The PAK3-Nck2 complex regulates post-synaptic transmission independently of spine dynamics. Significance: This opens perspectives in understanding the PAK3 implication in synaptic plasticity and mental retardation.