Huntingtin Interacting Protein 1 Is a Clathrin Coat Binding Protein Required for Differentiation of late Spermatogenic Progenitors

Rao, Dinesh S.; Chang, Jenny C.; Kumar, Priti D.; Mizukami, Ikuko F.; Smithson, Glennda; Bradley, Sarah V.; Parlow, Albert F.; Ross, Theodora S.

doi:10.1128/mcb.21.22.7796-7806.2001

Cited by 71 publications

(65 citation statements)

References 31 publications

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“…Hip1-deficient mice showed testicular degeneration with increased apoptosis of postmeiotic spermatids (26) and cataracts caused by cell death in the lens (27). In addition, caspase-9-dependent apoptosis was observed when a dominant-negative Hip1 construct was expressed in 293T cells (28).…”

Section: Figurementioning

confidence: 99%

Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice

et al. 2008

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Huntingtin interacting protein 1 related (Hip1r) is an F-actin-and clathrin-binding protein involved in vesicular trafficking. In this study, we demonstrate that Hip1r is abundantly expressed in the gastric parietal cell, predominantly localizing with F-actin to canalicular membranes. Hip1r may provide a critical function in vivo, as demonstrated by extensive changes to parietal cells and the gastric epithelium in Hip1r-deficient mice. Electron microscopy revealed abnormal apical canalicular membranes and loss of tubulovesicles in mutant parietal cells, suggesting that Hip1r is necessary for the normal trafficking of these secretory membranes. Accordingly, acid secretory dynamics were altered in mutant parietal cells, with enhanced activation and acid trapping, as measured in isolated gastric glands. At the whole-organ level, gastric acidity was reduced in Hip1r-deficient mice, and the gastric mucosa was grossly transformed, with fewer parietal cells due to enhanced apoptotic cell death and glandular hypertrophy associated with cellular transformation. Hip1r-deficient mice had increased expression of the gastric growth factor gastrin, and mice mutant for both gastrin and Hip1r exhibited normalization of both proliferation and gland height. Taken together, these studies demonstrate that Hip1r plays a significant role in gastric physiology, mucosal architecture, and secretory membrane dynamics in parietal cells.

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Section: Figurementioning

confidence: 99%

Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice

et al. 2008

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“…Cbl-b is an E3 ubiquitin ligase that mono-ubiquitinates membrane receptors for recycling through clathrin vesicles. It is important to note that HIP1 (huntingtin interacting protein 1) is involved in the submembrane molecular structure of clathrincoated vesicles (Engqvist-Goldstein et al, 1999;Kim et al, 1999;Metzler et al, 2001;Rao et al, 2001;Waelter et al, 2001a,b;Legendre-Guillemin et al, 2005). The substrates of Cbl-b include the epidermal growth factor receptor, colony-stimulating factor 1 receptor, hepatocyte growth factor receptor/Met, and so on (Peschard and Park, 2003).…”

Section: Other Candidate Genes In the Polyq Pathologiesmentioning

confidence: 99%

The Induction Levels of Heat Shock Protein 70 Differentiate the Vulnerabilities to Mutant Huntingtin among Neuronal Subtypes

Tagawa¹,

Marubuchi²,

Qi³

et al. 2007

J. Neurosci.

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The reason why vulnerabilities to mutant polyglutamine (polyQ) proteins are different among neuronal subtypes is mostly unknown. In this study, we compared the gene expression profiles of three types of primary neurons expressing huntingtin (htt) or ataxin-1. We found that heat shock protein 70 (hsp70), a well known chaperone molecule protecting neurons in the polyQ pathology, was dramatically upregulated only by mutant htt and selectively in the granule cells of the cerebellum. Granule cells, which are insensitive to degeneration in the human Huntington's disease (HD) pathology, lost their resistance by suppressing hsp70 with siRNA, whereas cortical neurons, affected in human HD, gained resistance by overexpressing hsp70. This indicates that induction levels of hsp70 are a critical factor for determining vulnerabilities to mutant htt among neuronal subtypes. CAT (chloramphenicol acetyltransferase) assays showed that CBF (CCAAT box binding factor, CCAAT/enhancer binding protein ) activated, but p53 repressed transcription of the hsp70 gene in granule cells. Basal and mutant htt-induced expression levels of p53 were remarkably lower in granule cells than in cortical neurons, suggesting that different magnitudes of p53 are linked to distinct induction levels of hsp70. Surprisingly, however, heat shock factor 1 was not activated in granule cells by mutant htt. Collectively, different levels of hsp70 among neuronal subtypes might be involved in selective neuronal death in the HD pathology.

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“…The deletion of Gapds by gene targeting produces infertile male mice with profound defects in sperm motility (21). Generation of Hip1/Hip1r double-knockout mice leads to accelerated spine abnormalities and testicular degeneration (22). Similar Gapds and Hip1r MSY-RNA levels were found in the testes of wild-type and Gapds or Hip1/Hip1r null mice, whereas decreases of up to 6-fold were seen for the Gapds and Hip1r mRNAs by real-time PCR assay.…”

Section: The Amounts Of Most Msy-rnas Change Little During Testicularmentioning

confidence: 90%

MIWI-independent small RNAs (MSY-RNAs) bind to the RNA-binding protein, MSY2, in male germ cells

Medvedev

Yang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The germ cell-specific DNA/RNA-binding protein MSY2 binds small RNAs (MSY-RNAs) that are Ϸ25-31 nt in length, often initiate with a 5 adenine, and are expressed in both germ cells and somatic cells. MSY-RNA levels do not decrease in Miwi or Msy2 null mice. Most MSY-RNAs map within annotated genes, but some are PIWIinteracting RNA (piRNA)-like and map to piRNA clusters. MSY-RNAs are in both nuclei and cytoplasm. In nuclei, MSY-RNAs are enriched in chromatin, and in the cytoplasm they are detected in both ribonucleoproteins and polysomes.noncoding RNA ͉ RNA-protein interactions ͉ Y box proteins ͉ spermatogenesis N oncoding RNAs play important roles in regulating gene expression and development (1). Among the many classes of small noncoding RNAs are micro RNAs (miRNAs), siRNAs, endo-siRNAs, and PIWI-interacting RNAs (piRNAs) (reviewed in refs. 2-4). piRNAs are an extremely abundant group of germ cell RNAs of Ϸ30 nt that often initiate with a 5Ј uracil and require members of the PIWI family of proteins for their biogenesis (4, 5). Based on sequence and their time of expression, piRNAs in mice have been classified as MILI (PIWIL2)-associated, MIWI2 (PIWIL4)-associated, or MIWI (PIWIL1)-associated piRNAs (4, 6). They are believed to be transcribed from long precursor RNAs and processed by a Dicerindependent mechanism (4, 6). Although some mammalian piRNAs share features with the Drosophila repeat-sequence repeat associated small interfering RNA (rasiRNAs) that are proposed to control transposable elements (6-8), the large number, variable sequences, and nuclear localization of mammalian piRNAs suggest additional cellular functions (9, 10).The germ cell-specific DNA/RNA-binding protein MSY2 is a member of a Y box family of cold shock domain proteins (11). It is solely expressed in male and female germ cells and necessary for fertility (12). In the male, the absence of MSY2 leads to precocious destabilization of germ cell mRNAs (12). MSY2 serves as a coactivator of transcription, binding to the DNA sequence CTGATTGGC/TC/TAA in the promoters of genes transcribed in germ cells, thereby linking transcription with mRNA storage/stabilization (11). Suppressive subtractive hybridization studies reveal that of the nearly 100 MSY2 bound/ nonbound mRNAs analyzed, many mRNAs encoding male gamete-specific and translationally delayed proteins are bound by MSY2 (11). In addition, MSY2 also binds in vitro to the piRNA, gsRNA10 (13).Here, we describe a previously uncharacterized class of small RNAs (MSY-RNAs) from the mouse testis that are bound by MSY2. MSY-RNAs are Ϸ25-31 nt, often initiate with a 5Ј adenine, and are expressed throughout germ cell differentiation and in somatic cells. The majority of the MSY-RNAs are derived from annotated genes, and some MSY-RNAs are piRNAs or piRNA-like. MSY-RNA levels are not altered in MIWI or MSY2 null mice. Results and Discussion MSY2 Selectively Binds a Previously Uncharacterized Population ofϷ30-Nucleotide RNAs. Because in vitro RNA gel shift assays revealed that MSY2 binds to the piRNA, gsRN...

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Huntingtin Interacting Protein 1 Is a Clathrin Coat Binding Protein Required for Differentiation of late Spermatogenic Progenitors

Cited by 71 publications

References 31 publications

Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice

Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice

The Induction Levels of Heat Shock Protein 70 Differentiate the Vulnerabilities to Mutant Huntingtin among Neuronal Subtypes

MIWI-independent small RNAs (MSY-RNAs) bind to the RNA-binding protein, MSY2, in male germ cells

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