| Texto completo | |
| Autor(es): |
Meneghetti, Maria C. Z.
;
Cavalheiro, Renan P.
;
Yates, Edwin A.
;
Nader, Helena B.
;
Lima, Marcelo A.
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FEBS Journal; v. N/A, p. 14-pg., 2025-01-13. |
| Resumo | |
Vesicle trafficking is pivotal in heparan sulfate (HS) biosynthesis, influencing its spatial and temporal regulation within distinct Golgi compartments. This regulation modulates the sulfation pattern of HS, which is crucial for governing various biological processes. Here, we investigate the effects of silencing Rab1A and Rab2A expression on the localisation of 3-O-sulfotransferase-5 (3OST5) within Golgi compartments and subsequent alterations in HS structure and levels. Interestingly, silencing Rab1A led to a shift in 3OST5 localization towards the trans-Golgi, resulting in increased HS levels within 24 and 48 h, while silencing Rab2A caused 3OST5 accumulation in the cis-Golgi, with a delayed rise in HS content observed after 48 h. Furthermore, a compensatory mechanism was evident in Rab2A-silenced cells, where increased Rab1A protein expression was detected. This suggests a dynamic interplay between Rab1A and Rab2A in maintaining the fine balance of vesicle trafficking processes involved in HS biosynthesis. Additionally, we demonstrate that the trafficking of 3OST5 in COPI vesicles is facilitated by GOLPH3 protein. These findings identify novel vesicular transport mechanisms regulating HS biosynthesis and reveal a compensatory relationship between Rab1A and Rab2A in maintaining baseline HS production. (AU) | |
| Processo FAPESP: | 20/04899-1 - Interação da proteína de superfície (spike protein) do SARS-CoV-2 com heparina: potencial terapêutico |
| Beneficiário: | Helena Bonciani Nader |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/15369-6 - Geração de linhagens celulares utilizando o sistema CRISPR-Cas9: oportunidade de estudo de mecanismos de neurodegeneração em doenças raras e desenvolvimento de novos tratamentos com impacto para o sistema público de saúde |
| Beneficiário: | Helena Bonciani Nader |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/19298-6 - Desvendando a influência do tráfego vesicular na regulação da biossíntese do heparam sulfato |
| Beneficiário: | Maria Cecília Zorél Meneghetti |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 20/02577-7 - EMU concedido no processo 2015/03964-6: sistema cromatografia líquida AKTA pure 25 M |
| Beneficiário: | Helena Bonciani Nader |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |