PMID:11604514

Citation	Rao, DS, Chang, JC, Kumar, PD, Mizukami, I, Smithson, GM, Bradley, SV, Parlow, AF and Ross, TS (2001) Huntingtin interacting protein 1 Is a clathrin coat binding protein required for differentiation of late spermatogenic progenitors. Mol. Cell. Biol. 21:7796-806
Abstract	Huntingtin-interacting protein 1 (HIP1) interacts with huntingtin, the protein whose gene is mutated in Huntington's disease. In addition, a fusion between HIP1 and platelet-derived growth factor beta receptor causes chronic myelomonocytic leukemia. The HIP1 proteins, including HIP1 and HIP1-related (HIP1r), have an N-terminal polyphosphoinositide-interacting epsin N-terminal homology, domain, which is found in proteins involved in clathrin-mediated endocytosis. HIP1 and HIP1r also share a central leucine zipper and an actin binding TALIN homology domain. Here we show that HIP1, like HIP1r, colocalizes with clathrin coat components. We also show that HIP1 physically associates with clathrin and AP-2, the major components of the clathrin coat. To further understand the putative biological role(s) of HIP1, we have generated a targeted deletion of murine HIP1. HIP1(-/-) mice developed into adulthood, did not develop overt neurologic symptoms in the first year of life, and had normal peripheral blood counts. However, HIP1-deficient mice exhibited testicular degeneration with increased apoptosis of postmeiotic spermatids. Postmeiotic spermatids are the only cells of the seminiferous tubules that express HIP1. These findings indicate that HIP1 is required for differentiation, proliferation, and/or survival of spermatogenic progenitors. The association of HIP1 with clathrin coats and the requirement of HIP1 for progenitor survival suggest a role for HIP1 in the regulation of endocytosis.
Links	PubMed PMC99949 Online version:10.1128/MCB.21.22.7796-7806.2001
Keywords	Animals; Base Sequence; Carrier Proteins/genetics; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cell Differentiation; Cell Line, Transformed; Clathrin-Coated Vesicles/metabolism; DNA, Complementary; DNA-Binding Proteins; Gene Targeting/methods; Humans; Huntington Disease/metabolism; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Sequence Analysis, Protein; Spermatogenesis/physiology; Spermatozoa/cytology; Stem Cells; Time Factors; Tumor Cells, Cultured; Vesicular Transport Proteins
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