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Publication : Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice.

First Author  Yang Y Year  2005
Journal  Exp Cell Res Volume  304
Issue  1 Pages  50-8
PubMed ID  15707573 Mgi Jnum  J:98059
Mgi Id  MGI:3577003 Doi  10.1016/j.yexcr.2004.11.014
Citation  Yang Y, et al. (2005) Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice. Exp Cell Res 304(1):50-8
abstractText  The mouse fidget mutation is an autosomal recessive mutation that renders reduced or absent semicircular canals, microphthalmia, and various skeletal abnormalities to affected mice. We previously identified the defective gene which encodes fidgetin, a new member of the ATPases associated with diverse cellular activities (AAA proteins). Here, we report on the subcellular localization of fidgetin as well as that of two closely related proteins, fidgetin-like 1 and fidgetin-like 2. Epitope-tagging and immunostaining revealed that both fidgetin and fidgetin-like 2 were predominantly localized to the nucleus, whereas fidgetin-like 1 was both nuclear and cytoplasmic. Furthermore, deletion studies identified a putative bipartite nuclear localization signal in the middle portion of the fidgetin protein. Since AAA proteins are known to form functional hetero- or homo-hexamers, we used reciprocal immunoprecipitation to examine the potential interaction among these proteins. We found that fidgetin interacted with itself and this specific interaction was abolished when either the N- or C-terminus of the protein was truncated. Taken together, our results suggest that fidgetin is a nuclear AAA-family protein with the potential to form homo-oligomers, thus representing the first step towards the elucidation of fidgetin's cellular function and the disease mechanism in fidget mutant mice.
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