Interaction of ADP Ribosylation Factor Like Proteins with Polycystin-1

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIDDK	CELLBIO-16

Authors

• T Wang
• K.L Gorelick
• G.G Germino

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder, characterized by bilateral renal cysts and cysts in other organs. Mutations in polycystin-1 cause 85% of ADPKD. The polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain is found in the first intracellular loop of polycystin-1 and its family members. It is a highly conserved, signature motif of the polycystin-1 family of proteins, however, the function of the PLAT in polycystin-1 is not clear. We used the PLAT domain of a related polycystin-1 family member, PKDREJ, as bait in a yeast two-hybrid screen. Analysis of the resultant clones result in tour target protein as ADP ribosylation factor like 4 (Arl4). Arl proteins belong to the small GTPase superfamily and are suggested to have roles in vesicle formation and trafficking. Arl3, Arl6 and Arl13b, in particular, are involved in the cilia related dysfunction and ciliopathies including ADPKD. We have show that Arl4 and Arl13b but not Arl3 are interact with polycystin-1 in HEK 293 cells by co-immunoprecipitation. Co-localization of polycystin-1 and Arl proteins are also observed. The function significance of this co-localization is under current investigation. In summary, our data suggests that a possible interaction of Arl proteins with of polycystin-1 in the intracellular trafficking.

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