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1.
J Cell Sci ; 136(10)2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37096733

RESUMO

GIPC3 has been implicated in auditory function. Here, we establish that GIPC3 is initially localized to the cytoplasm of inner and outer hair cells of the cochlea and then is increasingly concentrated in cuticular plates and at cell junctions during postnatal development. Early postnatal Gipc3KO/KO mice had mostly normal mechanotransduction currents, but had no auditory brainstem response at 1 month of age. Cuticular plates of Gipc3KO/KO hair cells did not flatten during development as did those of controls; moreover, hair bundles were squeezed along the cochlear axis in mutant hair cells. Junctions between inner hair cells and adjacent inner phalangeal cells were also severely disrupted in Gipc3KO/KO cochleas. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. Immunoaffinity purification of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks and the cuticular plate. Several of immunoprecipitated proteins contained GIPC family consensus PDZ-binding motifs (PBMs), including MYO18A, which bound directly to the PDZ domain of GIPC3. We propose that GIPC3 and MYO6 couple to PBMs of cytoskeletal and cell junction proteins to shape the cuticular plate.


Assuntos
Mecanotransdução Celular , Domínios PDZ , Camundongos , Animais , Células Ciliadas Auditivas Internas/metabolismo , Citoesqueleto/metabolismo , Células Ciliadas Auditivas Externas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Miosinas/genética , Miosinas/metabolismo
2.
bioRxiv ; 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36909580

RESUMO

GIPC3 has been implicated in auditory function. Initially localized to the cytoplasm of inner and outer hair cells of the cochlea, GIPC3 increasingly concentrated in cuticular plates and at cell junctions during postnatal development. Early postnatal Gipc3 KO/KO mice had mostly normal mechanotransduction currents, but had no auditory brainstem response at one month of age. Cuticular plates of Gipc3 KO/KO hair cells did not flatten during development as did those of controls; moreover, hair bundles were squeezed along the cochlear axis in mutant hair cells. Junctions between inner hair cells and adjacent inner phalangeal cells were also severely disrupted in Gipc3 KO/KO cochleas. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. Immunoaffinity purification of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks, and the cuticular plate. Several of immunoprecipitated proteins contained GIPC-family consensus PDZ binding motifs (PBMs), including MYO18A, which binds directly to the PDZ domain of GIPC3. We propose that GIPC3 and MYO6 couple to PBMs of cytoskeletal and cell-junction proteins to shape the cuticular plate. Summary statement: The PDZ-domain protein GIPC3 couples the molecular motors MYO6 and MYO18A to actin cytoskeleton structures in hair cells. GIPC3 is necessary for shaping the hair cell’s cuticular plate and hence the arrangement of the stereocilia in the hair bundle.

3.
PLoS One ; 15(3): e0230308, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176723

RESUMO

Top predators can exert strong influences on community structure and function, both via direct, consumptive effects, as well as through non-consumptive, fear-based effects (i.e. predation risk). However, these effects are challenging to quantify, particularly for mobile predators in marine ecosystems. To advance this field of research, here we used baited remote underwater video stations (BRUVs) to assess how the behavior of mobile fish species off Cape Cod, Massachusetts, was affected by exposure to large sharks. We categorized sites into three levels of differential shark predation exposure (white sharks, Carcharodon carcharias) and quantified the relative abundance and arrival times (elapsed time before appearing on screen) for six mobile fish prey groups to the BRUV stations. Increased large shark exposure was associated with a decrease in overall prey abundance, but the overall response was prey group-specific. Foraging of smooth dogfish, a likely important prey item for large sharks in the system, was significantly reduced in areas frequented by white sharks. Specifically, the predicted probabilities of smooth dogfish bait contacts or bite attempts occurring were reduced by factors of 5.7 and 8.4, respectively, in areas of high exposure as compared to low exposure. These modifications were underscored by a decrease in smooth dogfish abundance in areas of high exposure as well. Our results suggest that populations of large, roving sharks may induce food-related costs in prey. We discuss the implications of this work within the context of the control of risk (COR) hypothesis, for the purposes of advancing our understanding of the ecological role and effects of large sharks on coastal marine ecosystems.


Assuntos
Ecossistema , Exposição Ambiental , Peixes/fisiologia , Movimento , Comportamento Predatório/fisiologia , Tubarões/fisiologia , Animais , Geografia
4.
J Cell Biol ; 216(11): 3861-3881, 2017 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-28899994

RESUMO

Control of the dimensions of actin-rich processes like filopodia, lamellipodia, microvilli, and stereocilia requires the coordinated activity of many proteins. Each of these actin structures relies on heterodimeric capping protein (CAPZ), which blocks actin polymerization at barbed ends. Because dimension control of the inner ear's stereocilia is particularly precise, we studied the CAPZB subunit in hair cells. CAPZB, present at ∼100 copies per stereocilium, concentrated at stereocilia tips as hair cell development progressed, similar to the CAPZB-interacting protein TWF2. We deleted Capzb specifically in hair cells using Atoh1-Cre, which eliminated auditory and vestibular function. Capzb-null stereocilia initially developed normally but later shortened and disappeared; surprisingly, stereocilia width decreased concomitantly with length. CAPZB2 expressed by in utero electroporation prevented normal elongation of vestibular stereocilia and irregularly widened them. Together, these results suggest that capping protein participates in stereocilia widening by preventing newly elongating actin filaments from depolymerizing.


Assuntos
Proteína de Capeamento de Actina CapZ/metabolismo , Células Ciliadas Auditivas/metabolismo , Animais , Limiar Auditivo , Comportamento Animal , Tronco Encefálico/metabolismo , Tronco Encefálico/fisiopatologia , Proteína de Capeamento de Actina CapZ/deficiência , Proteína de Capeamento de Actina CapZ/genética , Embrião de Galinha , Cílios/metabolismo , Cílios/ultraestrutura , Potenciais Evocados Auditivos do Tronco Encefálico , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Células Ciliadas Auditivas/ultraestrutura , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Emissões Otoacústicas Espontâneas , Fenótipo , Potenciais Evocados Miogênicos Vestibulares , Vestíbulo do Labirinto/metabolismo , Vestíbulo do Labirinto/fisiopatologia
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