GAR22? regulates cell migration, sperm motility, and axoneme structure.

ABSTRACT: Spatiotemporal cytoskeleton remodeling is pivotal for cell adhesion and migration. Here we investigated the function of Gas2-related protein on chromosome 22 (GAR22?), a poorly characterized protein that interacts with actin and microtubules. Primary and immortalized GAR22?(-/-) Sertoli cells moved faster than wild-type cells. In addition, GAR22?(-/-) cells showed a more prominent focal adhesion turnover. GAR22? overexpression or its reexpression in GAR22?(-/-) cells reduced cell motility and focal adhesion turnover. GAR22?-actin interaction was stronger than GAR22?-microtubule interaction, resulting in GAR22? localization and dynamics that mirrored those of the actin cytoskeleton. Mechanistically, GAR22? interacted with the regulator of microtubule dynamics end-binding protein 1 (EB1) via a novel noncanonical amino acid sequence, and this GAR22?-EB1 interaction was required for the ability of GAR22? to modulate cell motility. We found that GAR22? is highly expressed in mouse testes, and its absence resulted in reduced spermatozoa generation, lower actin levels in testes, and impaired motility and ultrastructural disorganization of spermatozoa. Collectively our findings identify GAR22? as a novel regulator of cell adhesion and migration and provide a foundation for understanding the molecular basis of diverse cytoskeleton-dependent processes.

SUBMITTER: Gamper I 

PROVIDER: S-EPMC4713131 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other