Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.4.4 (
kinesin
)
5,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endosomal sorting of internalized cell surface receptors to the lysosomal pathway plays a crucial role in the control of cell signaling and function. Here we report the identification of GABA(A) receptor interacting factor-1 (GRIF1), a recently discovered protein of unknown function, as a new regulator of endosome-to-lysosome trafficking. Yeast two-hybrid screen and co-immunoprecipitation analysis reveal that GRIF1 interacts with
hepatocyte growth factor-regulated tyrosine kinase substrate
(
Hrs
), an essential component of the endosomal sorting machinery. We have mapped the binding domains of GRIF1 and
Hrs
that mediate their association and shown the colocalization of GRIF1 with
Hrs
on early endosomes. Like
Hrs
, both overexpression and siRNA-mediated depletion of GRIF1 inhibit the degradation of internalized epidermal growth factor receptors and block the trafficking of the receptors from early endosomes to the lysosomal pathway. Our results indicate, for the first time, a functional role for GRIF1 in the regulation of endosomal trafficking. Interestingly, overexpression of full-length GRIF1, but not the
Hrs
- or
kinesin
-interacting GRIF1 deletion mutants, causes a perinuclear clustering of early endosomes. Our findings suggest that GRIF1 may also participate in microtubule-based transport of early endosomes by acting as an adaptor linking
Hrs
-containing endosomes to
kinesin
.
...
PMID:GRIF1 binds Hrs and is a new regulator of endosomal trafficking. 1706 40
