RESUMO
The Arf-like protein Arl13b has been implicated in ciliogenesis and Sonic hedgehog signaling. Furthermore, we have previously shown that it regulates endocytic recycling traffic and interacts with actin. Herein, we report that the non-muscle myosin heavy chain IIA, also known as Myh9, is an Arl13b effector. Moreover, we found that both proteins localized to circular dorsal ruffles (CDRs) induced by platelet-derived growth factor stimulation and are required for their formation. CDRs are ring-shaped actin-dependent structures formed on the dorsal cell surface and are involved in diverse processes, such as macropinocytosis, integrin recycling, internalization of receptor tyrosine kinases and cell migration. We found that Arl13b or Myh9 silencing impaired cell migration, suggesting that Arl13b is required for this function through the interaction with Myh9. Moreover, Arl13b silencing impaired neural crest cell migration in zebrafish embryos. Furthermore, we showed that Arl13b is required for the formation of CDRs in migrating cells. Thus, our results indicate a new role for Arl13b in actin cytoskeleton remodeling through the interaction with Myh9, by driving the formation of CDRs necessary for cell migration.
Assuntos
Fatores de Ribosilação do ADP/metabolismo , Movimento Celular , Extensões da Superfície Celular/metabolismo , Miosina não Muscular Tipo IIA/metabolismo , Animais , Endossomos/metabolismo , Células HeLa , Humanos , Camundongos , Cadeias Pesadas de Miosina , Células NIH 3T3 , Pinocitose , Transporte Proteico , Peixe-ZebraRESUMO
Rab and ADP-ribosylation factor (Arf) family proteins are master regulators of membrane trafficking and are involved in all steps of vesicular transport. These families of small guanine-nucleotide-binding (G) proteins are well suited to regulate membrane trafficking processes since their nucleotide state determines their conformation and the capacity to bind to a multitude of effectors, which mediate their functions. In recent years, several inherited diseases have been associated with mutations in genes encoding proteins belonging to these two families or in proteins that regulate their GTP-binding cycle. The genetic diseases that are caused by defects in Rabs, Arfs or their regulatory proteins are heterogeneous and display diverse symptoms. However, these diseases mainly affect two types of subcellular compartments, namely lysosome-related organelles and cilia. Also, several of these diseases affect the nervous system. Thus, the study of these diseases represents an opportunity to understand their etiology and the molecular mechanisms involved, as well as to develop novel therapeutic strategies.
Assuntos
Fatores de Ribosilação do ADP/metabolismo , Doenças Genéticas Inatas/genética , Proteínas rab de Ligação ao GTP/metabolismo , Fatores de Ribosilação do ADP/genética , Animais , Doenças Genéticas Inatas/etiologia , Doenças Genéticas Inatas/metabolismo , Humanos , Mutação , Transporte Proteico , Proteínas rab de Ligação ao GTP/genéticaRESUMO
Striae are common dermal lesions associated with physiological and psychological alterations, affecting the quality of life. This proposed randomized controlled trial protocol will evaluate the clinical efficacy and treatment safety of fractional CO2 laser versus fractional radiofrequency (FRF) in clinical trials. We will randomly allocate 60 subjects who present abdominal striae into two different groups for the treatment, which will be performed once a month for a 3-month period. The results will be assessed by quartile scoring criteria; by comparing digital photos taken before and after each treatment; and also, by the measurement of cutaneous temperature, skin pH, and elasticity before and after the treatment. This paper describes the rationale and the design of the randomized controlled trial, which may provide evidence for clinical application of the methodology and the quality related to the efficacy and safety of fractional CO2 laser versus the FRF protocol for striae treatment.
RESUMO
Striae (striae cutis distensae) are a common disfiguring skin condition, characterised by the appearance of linear bands on the skin, with an atrophic look. The striae development is still unknown, being more common in women than in men. The prevalence of this condition ranges from 50% to 90%. Regarding treatment, there are various treatment strategies currently available for stretch marks, including topical preparations such as tretinoin and glycolic acid, and also laser. The goal of this work is to discover the main treatments available for striae management. For that, a search was performed based on the definition of specific scientific keywords, by exploring PubMed, ScienceDirect and Biblioteca Virtual em Saúde (BVS). MeSH thesaurus (Medical Subject Headings) descriptors were used. The results indicate that, to date, no treatment is fully effective. More clinical trials are needed to validate the efficacy of these therapies and their long-term use in this type of skin lesion.