Regulation of Liprin-α phase separation by CASK is disrupted by a mutation in its CaM kinase domain.

ABSTRACT: CASK is a unique membrane-associated guanylate kinase (MAGUK) because of its Ca²⁺/calmodulin-dependent kinase (CaMK) domain. We describe four male patients with a severe neurodevelopmental disorder with microcephaly carrying missense variants affecting the CaMK domain. One boy who carried the p.E115K variant and died at an early age showed pontocerebellar hypoplasia (PCH) in addition to microcephaly, thus exhibiting the classical MICPCH phenotype observed in individuals with CASK loss-of-function variants. All four variants selectively weaken the interaction of CASK with Liprin-α2, a component of the presynaptic active zone. Liprin-α proteins form spherical phase-separated condensates, which we observe here in Liprin-α2 overexpressing HEK293T cells. Large Liprin-α2 cluste

SUBMITTER: Tibbe D 

PROVIDER: S-EPMC9500383 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature