Localization, traffic and function of Rab34 in adipocyte lipid and endocrine functions.

Autor: López-Alcalá J; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain., Gordon A; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain. v92becoa@uco.es., Trávez A; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain., Tercero-Alcázar C; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain., Correa-Sáez A; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain., González-Rellán MJ; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain.; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Rangel-Zúñiga OA; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain.; Lipids and Atherosclerosis Unit, IMIBIC/University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain., Rodríguez A; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain.; Metabolic Research Laboratory, Department of Endocrinology & Nutrition, Clinic, University of Navarra, IdiSNA, Pamplona, Spain., Membrives A; Department of Medical-Surgical Specialties, University of Córdoba (UCO), Reina Sofia University Hospital (HURS), Córdoba, Spain., Frühbeck G; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain.; Metabolic Research Laboratory, Department of Endocrinology & Nutrition, Clinic, University of Navarra, IdiSNA, Pamplona, Spain., Nogueiras R; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain.; Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Calzado MA; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain., Guzmán-Ruiz R; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain.; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain., Malagón MM; Department of Cell Biology, Physiology, and Immunology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), Reina Sofía University Hospital (HURS), Córdoba, Spain. bc1mapom@uco.es.; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, Spain. bc1mapom@uco.es.
Jazyk: angličtina
Zdroj: Journal of biomedical science [J Biomed Sci] 2024 Jan 05; Vol. 31 (1), pp. 2. Date of Electronic Publication: 2024 Jan 05.
DOI: 10.1186/s12929-023-00990-8
Abstrakt: Background: Excessive lipid accumulation in the adipose tissue in obesity alters the endocrine and energy storage functions of adipocytes. Adipocyte lipid droplets represent key organelles coordinating lipid storage and mobilization in these cells. Recently, we identified the small GTPase, Rab34, in the lipid droplet proteome of adipocytes. Herein, we have characterized the distribution, intracellular transport, and potential contribution of this GTPase to adipocyte physiology and its regulation in obesity.
Methods: 3T3-L1 and human primary preadipocytes were differentiated in vitro and Rab34 distribution and trafficking were analyzed using markers of cellular compartments. 3T3-L1 adipocytes were transfected with expression vectors and/or Rab34 siRNA and assessed for secretory activity, lipid accumulation and expression of proteins regulating lipid metabolism. Proteomic and protein interaction analyses were employed for the identification of the Rab34 interactome. These studies were combined with functional analysis to unveil the role played by the GTPase in adipocytes, with a focus on the actions conveyed by Rab34 interacting proteins. Finally, Rab34 regulation in response to obesity was also evaluated.
Results: Our results show that Rab34 localizes at the Golgi apparatus in preadipocytes. During lipid droplet biogenesis, Rab34 translocates from the Golgi to endoplasmic reticulum-related compartments and then reaches the surface of adipocyte lipid droplets. Rab34 exerts distinct functions related to its intracellular location. Thus, at the Golgi, Rab34 regulates cisternae integrity as well as adiponectin trafficking and oligomerization. At the lipid droplets, this GTPase controls lipid accumulation and lipolysis through its interaction with the E1-ubiquitin ligase, UBA1, which induces the ubiquitination and proteasomal degradation of the fatty acid transporter and member of Rab34 interactome, FABP5. Finally, Rab34 levels in the adipose tissue and adipocytes are regulated in response to obesity and related pathogenic insults (i.e., fibrosis).
Conclusions: Rab34 plays relevant roles during adipocyte differentiation, including from the regulation of the oligomerization (i.e., biological activity) and secretion of a major adipokine with insulin-sensitizing actions, adiponectin, to lipid storage and mobilization from lipid droplets. Rab34 dysregulation in obesity may contribute to the altered adipokine secretion and lipid metabolism that characterize adipocyte dysfunction in conditions of excess adiposity.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje