G-protein coupled receptor (GPCR) kinase interacting proteins 1 and 2 (GIT-1 and GIT-2) are highly conserved,
ubiquitous scaffold proteins involved in localized
signaling to help regulate focal contact assembly and
cytoskeletal dynamics. GIT proteins contain multiple
interaction domains that allow interaction with small
GTPases (including ARF, Rac and cdc42), kinases (such as
PAK and MEK), the Rho family GEF PIX, and the focal
adhesion protein paxillin (reviewed in 1). GIT-1 is
localized to focal adhesions, cytoplasmic complexes and
membrane protrusions, and regulates cell protrusion
formation and cell migration (2). GIT-1 has also been
implicated in neuronal functions including synapse
formation (3) and the pathology of Huntington disease
(4). Huntington disease is a genetic neurodegenerative
condition involving a mutation in the huntington gene.
The huntington gene product (htt) is ubiquitinated and
degraded in human Huntington disease brains (5). Htt
interacts directly with GIT-1 causing enhanced htt
proteolysis, indicating that GIT-1 distribution and function may contribute to Huntington disease pathology
(4).