Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

Weil, Dominique; Lévy, Gallia; Sahly, Iman; Levi‐Acobas, Fabienne; Blanchard, Stéphane; El-Amraoui, Aziz; Crozet, Fabien; Piégay, Hervé; Abitbol, Marc; Petit, Christine

doi:10.1073/pnas.93.8.3232

Cited by 166 publications

(154 citation statements)

References 34 publications

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“…Mutations in membrane proteins such as RDS and the photon receptor RHO are known to cause RP. Several genes related to protein trafficking and the cytoskeletal structures, such as FSCN2, that bind to actin (39,40) and microtubule-associated RP1 (41), as well as MYO7A (42)(43)(44)(45) involved in intracellular trafficking, have also been reported as RP-causative genes. Ub modification is known to be important for the quality control, internalization, and multivesicular body sorting of membrane proteins.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin Ligase Activity of Cul3-KLHL7 Protein Is Attenuated by Autosomal Dominant Retinitis Pigmentosa Causative Mutation

Kigoshi

Tsuruta

Chiba

2011

Journal of Biological Chemistry

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Substrate-specific protein degradation mediated by the ubiquitin proteasome system (UPS) is crucial for the proper function of the cell. Proteins are specifically recognized and ubiquitinated by the ubiquitin ligases (E3s) and are then degraded by the proteasome. BTB proteins act as the substrate recognition subunit that recruits their cognate substrates to the Cullin 3-based multisubunit E3s. Recently, it was reported that missense mutations in KLHL7, a BTB-Kelch protein, are related to autosomal dominant retinitis pigmentosa (adRP). However, the involvement of KLHL7 in the UPS and the outcome of the adRP causative mutations were unknown. In this study, we show that KLHL7 forms a dimer, assembles with Cul3 through its BTB and BACK domains, and exerts E3 activity. Lys-48-linked but not Lys-63-linked polyubiquitin chain co-localized with KLHL7, which increased upon proteasome inhibition suggesting that KLHL7 mediates protein degradation via UPS. An adRP-causative missense mutation in the BACK domain of KLHL7 attenuated only the Cul3 interaction but not dimerization. Nevertheless, the incorporation of the mutant as a heterodimer in the Cul3-KLHL7 complex diminished the E3 ligase activity. Together, our results suggest that KLHL7 constitutes a Cul3-based E3 and that the disease-causing mutation inhibits ligase activity in a dominant negative manner, which may lead to the inappropriate accumulation of the substrates targeted for proteasomal degradation.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin Ligase Activity of Cul3-KLHL7 Protein Is Attenuated by Autosomal Dominant Retinitis Pigmentosa Causative Mutation

Kigoshi

Tsuruta

Chiba

2011

Journal of Biological Chemistry

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“…Four of the Tetrahymena myosins contain both MyTH4 and FERM. The MyTH4/FERM coupling exists in at least four other classes of myosins-VII [Chen et al, 1996, Weil et al, 1996, X [Berg et al, 2000], XII [Berg et al, 2001] and XV [Wang et al, 1998]-and in the divergent myoG in Dictyostelium [Titus, 2003]. In Myosins VII and XV, coupling of FERM and MyTH4 has been duplicated.…”

Section: Myosin Genes Encode Divergent Unconventional Myosins In Tetrmentioning

confidence: 99%

Myosin genes in Tetrahymena

Williams

Gavin

2005

Cell Motil. Cytoskeleton

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“…The variant of this gene was shown to be associated with type 2 diabetes mellitus in Japanese individuals, with the A1 allele (21 CA repeats) representing a risk factor for this condition (31). Although mutations in certain myosins can cause diseases in humans and mice (32), the myosin-VIIb gene (MYO7B) has not been related to human disease. An antibody to MYO7B labeled proximal tubule cells of the kidney, specifically the distal tips of apical microvilli on these transporting epithelial cells (33).…”

Section: Discussionmentioning

confidence: 99%

Association of gene polymorphisms with chronic kidney disease in Japanese individuals

Yamada¹

2009

Int J Mol Med

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Abstract. Chronic kidney disease (CKD) is recognized as a risk factor not only for end-stage renal disease but also for cardiovascular disease. Early detection and treatment of CKD is a likely key factor for prevention of its complications. Although genetic linkage analyses and association studies have implicated several loci and candidate genes in predisposition to CKD, the genes that underlie genetic susceptibility to this condition have remained largely unknown. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in Japanese individuals. The study population comprised 4,829 Japanese individuals (2,697 men, 2,132 women), including 757 subjects with CKD [464 men, 293 women; estimated glomerular filtration rate (eGFR) <50 ml min 1.73 m -2 ] and 4,072 controls (2,233 men, 1,839 women; eGFR ≥60 ml min 1.73 m -2 ). The genotypes for 40 polymorphisms of 39 candidate genes were determined. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that six polymorphisms of F10, PITRM1, PCSK2, JPH3, MYO7B, and AKAP12 were related (P<0.05) to the prevalence of CKD. Among these polymorphisms, the C→T polymorphism of F10 (rs5962) was most significantly associated with this condition. Determination of genotypes for the C→T polymorphism of F10 may prove informative for assessment of genetic risk for CKD in Japanese individuals.

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Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

Cited by 166 publications

References 34 publications

Ubiquitin Ligase Activity of Cul3-KLHL7 Protein Is Attenuated by Autosomal Dominant Retinitis Pigmentosa Causative Mutation

Ubiquitin Ligase Activity of Cul3-KLHL7 Protein Is Attenuated by Autosomal Dominant Retinitis Pigmentosa Causative Mutation

Myosin genes in Tetrahymena

Association of gene polymorphisms with chronic kidney disease in Japanese individuals

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