Vangl2 regulation in a mammalian model for planar polarity

来源 :中国神经科学学会第九届全国学术会议暨第五届会员代表大会 | 被引量 : 0次 | 上传用户:nihaobaobeisss
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  Vangl2 is one of the central proteins controlling the establishment of Planar Cell Polarity in different tissues and species.Moreover, results in both flies and mammals suggest that that the localization of Vangl2 protein to specific intracellular microdomains is crucial for normal function.However, the molecular mechanisms that control Vangl2 trafficking within a cell are largely unknown.Here, we identify a new binding partner for Vangl2, G-protein signaling-GAIP-interacting protein 1 (GIPC1).We show that the central PDZ domain of GtPC1 directly associates with the last 12 amino acids of Vangl2, and that GIPC 1, along with the motor protein Myosin Ⅵ (MyoⅥ), co-localizes with Vangl2 in endosomal clusters.We show that a GIPC1/MyoⅥ complex regulates the levels of Vangl2 at the plasma membrane.Consistent with this result, high resolution imaging by STED microscopy reveals a depletion of Vangl2 in the proximal membrane of hair cells, a location with a large accumulation of GIPC 1.Finally, downregulation of GIPC 1 in hair cells by shRNA in vitro or in utero leads to hair cell maturation defects, including defects in hair bundle orientation and integrity.These results demonstrate a role for GIPC 1 in the regulation of Vangl2 protein within developing hair cells.Moreover, morphological analysis of the effects of depletion of GIPC 1 indicates a broader role for this molecule in the development of both stereociliary bundles and planar cell polarization.
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