LRCH1 interferes with DOCK8-Cdc42-induced T cell migration and ameliorates experimental autoimmune encephalomyelitis.

ABSTRACT: Directional autoreactive CD4⁺ T cell migration into the central nervous system plays a critical role in multiple sclerosis. Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. Little is known about whether DOCK8 is related to multiple sclerosis (MS) and how to restrict its GEF activity. Using two screening systems, we found that LRCH1 competes with Cdc42 for interaction with DOCK8 and restrains T cell migration. In response to chemokine stimulation, PKCα phosphorylates DOCK8 at its three serine sites, promoting DOCK8 separation from LRCH1 and translocation to the leading edge to guide T cell migration. Point mutations at the DOCK8 serine sites block chemokine- and PKCα-induced T

SUBMITTER: Xu X 

PROVIDER: S-EPMC5206493 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature