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1.
Curr Biol ; 33(22): 4844-4856.e5, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37832552

RESUMO

After endocytosis, many plasma membrane components are recycled via membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here, we document an interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo, as does the loss of the PXF-1 target RAP-1. In some contexts, Rap-GTPases negatively regulate RhoA activity, suggesting a potential for Syndapin to regulate RhoA. Our results indicate that in the C. elegans intestine, RHO-1/RhoA is enriched on SDPN-1- and RAP-1-positive endosomes, and the loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well known for controlling actomyosin contraction cycles, although little is known about the effects of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1-positive endosomes, with two non-muscle myosin II heavy-chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, whereas depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating that actomyosin contractility controls recycling endosome function.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Actomiosina/metabolismo , Endocitose/fisiologia , Endossomos/metabolismo , Miosina Tipo II/metabolismo
2.
bioRxiv ; 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36909525

RESUMO

After endocytosis, many plasma membrane components are recycled via narrow-diameter membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that the F-BAR and SH3 domain Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here we sought to determine the significance of a predicted interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations we engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo , as does loss of the PXF-1 target RAP-1. Rap-GTPases have been shown in several contexts to negatively regulate RhoA activity. Our results show that RHO-1/RhoA is enriched on SDPN-1 and RAP-1 positive endosomes in the C. elegans intestine, and loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well-known for controlling actomyosin contraction cycles, although little is known of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1 positive endosomes, with two non-muscle myosin II heavy chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, while depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating actomyosin contractility in controlling recycling endosome function.

5.
9.
Rev. ADM ; 76(4): 234-241, jul.-ago 2019.
Artigo em Espanhol | LILACS | ID: biblio-1024069

RESUMO

Ética, moral y la deontología, se ocupan de un mismo objetivo: la valoración de lo bueno y de lo malo en la conducta humana. Sus enfoques del problema, no son totalmente iguales. La ética utiliza el análisis filosófico, ilumina el problema desde el ángulo axiológico, y a través de la especulación pura trata de establecer un deber ser de valor universal. La moral estudia las acciones humanas desde un punto de vista empírico, histórico, en la realidad de las diferentes culturas y teniendo en cuenta la diversidad de su idiosincrasia, trata de establecer juicios de valor adecuados a tales circunstancias. La deontología, fluctuando entre la ética y la moral y basándose en las conclusiones de ambas, se propone establecer las normas concretas que deben regir la conducta en situaciones determinadas, como puede ser el ejercicio de una profesión. La bioética establece los conceptos morales, éticos y racionales derivados en la interdisciplina de la ciencia y la biomedicina (AU)


Ethics, Moral and deontology, deal with the same objective: The assessment of good and evil in human behavior. Their approaches to the problem are not totally the same. Ethics uses philosophical analysis, illuminates the problem from the axiological angle, and through pure speculation tries to establish a duty of universal value. Morality studies human actions from an empirical, historical point of view, in the reality of different cultures and taking into account the diversity of their idiosyncrasy, tries to establish value judgments appropriate to such circumstances. Deontology, fluctuating between ethics and morals and based on the conclusions of both, it is proposed to establish the specific rules that should govern behavior in certain situations, such as the exercise of a profession. Bioethics establishes the moral, ethical and rational concepts derived in the interdiscipline of science and biomedicine (AU)


Assuntos
Sociedades Odontológicas , Códigos de Ética , Ética Odontológica , Prática Profissional/ética , Bioética , Teoria Ética , México , Moral
18.
Rev. ADM ; 75(3): 168-171, mayo-jun. 2018. ilus
Artigo em Espanhol | LILACS | ID: biblio-908937

RESUMO

La pérdida de dientes por lo general resulta en defectos de la cresta alveolar, dificultando la colocación de implantes. La corrección de estos defectos es un desafío para los cirujanos orales. La técnica de osteotomía segmentaria con injerto óseo interposicionado también conocida como osteotomía en «sándwich¼ ha demostrado ser efectiva para estos problemas. Se describe un caso clínico con la utilización de esta técnica para el aumento óseo vertical en la región anterior mandibular y la colocación de implantes (AU)


The loss of teeth usually results in defects of the alveolar ridge, making it diffi cult to place implants. The correction of these defects is a challenge for oral surgeons. The segmental sandwich technique with interpositional bone graft has proven to be predictable for these problems. We describe a clinical case with the use of this technique for vertical bone augmentation in the mandibular anterior region and the placement of dental implants (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Transplante Ósseo , Implantes Dentários , Osteotomia Mandibular , Procedimentos Cirúrgicos Pré-Protéticos Bucais , Prótese Dentária Fixada por Implante , México
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