Here, we describe for the first time a Leishmania specific gene encoding a large 610 amino-acid RAB GTPase (LmLRAB). LmLRAB displays high homologies with the RAB GTPase protein family between amino acids 34 and 284. It contains characteristic signatures of RAB proteins: 4 GTP binding domains, 5 RAB specific domains, 3 RAB subfamily-specific domains, and a prenylation site. lmlrab is a single copy gene, transcribed as a 3.5 kb mRNA, highly conserved in Leishmania species, and encodes a protein doublet of approximately 75 kDa. Immunofluorescence microscopy using LmLRAB-specific antibodies demonstrated that LmLRAB is confined in a structure adjacent to the kinetoplast probably corresponding to an early endosomal/golgi apparatus localization. Interestingly, using quantitative real-time RT-PCR, we showed that the lmlrab gene is up-regulated twice in amastigotes relative to promastigotes. These findings suggest that LmLRAB may play a potential role in Leishmania pathogenicity.
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http://dx.doi.org/10.1016/j.bbrc.2006.01.005 | DOI Listing |
Biochim Biophys Acta Mol Cell Res
January 2025
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia. Electronic address:
Cholesterol is an essential lipid that ensures the functional integrity of mammalian cells. Most cells acquire cholesterol via endocytosis of low-density lipoproteins (LDL). Upon reaching late endosomes/lysosomes (LE/Lys), incoming ligands, including LDL-derived cholesterol, are distributed to other organelles.
View Article and Find Full Text PDFJ Cell Sci
January 2025
Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Various N-terminal tags have often been used to identify the functions and localization of Rab small GTPases, but their impact on Rab proteins themselves has been poorly investigated. Here, we used a knockout (KO)-rescue approach to systematically evaluate the effect of N-terminal tagging of two Rabs, Rab10 and Rab27A, on Rab10-KO HeLa cells and Rab27A-deficient melanocytes (melan-ash cells), respectively. The results showed that all of the N-terminal-tagged Rab27A proteins mediated actin-based melanosome transport in the melan-ash cells, but none of the N-terminal-tagged Rab10 proteins fully rescued the defect in tubular endosome formation in the Rab10-KO cells.
View Article and Find Full Text PDFNat Commun
January 2025
Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
The heterodimeric Rab3GAP complex is a guanine nucleotide exchange factor (GEF) for the Rab18 GTPase that regulates lipid droplet metabolism, ER-to-Golgi trafficking, secretion, and autophagy. Why both subunits of Rab3GAP are required for Rab18 GEF activity and the molecular basis of how Rab3GAP engages and activates its cognate substrate are unknown. Here we show that human Rab3GAP is conformationally flexible and potentially autoinhibited by the C-terminal domain of its Rab3GAP2 subunit.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Ferroptosis is a newly identified programmed cell death induced by iron-driven lipid peroxidation and implicated as a potential approach for tumor treatment. However, emerging evidence indicates that hepatocellular carcinoma (HCC) cells are generally resistant to ferroptosis and the underlying molecular mechanism is poorly understood. Here, our study confirms that S100 calcium binding protein P (S100P), which is significantly up-regulated in ferroptosis-resistant HCC cells, efficiently inhibits ferroptosis.
View Article and Find Full Text PDFPathogens
December 2024
Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-shi 329-0498, Tochigi, Japan.
Hepatitis E virus (HEV) exists in two distinct forms: a non-enveloped form (neHEV), which is present in feces and bile, and a quasi-enveloped form (eHEV), found in circulating blood and culture supernatants. This study aimed to elucidate the roles of Ras-associated binding 13 (Rab13) and protein kinase A (PKA) in the entry mechanisms of both eHEV and neHEV, utilizing small interfering RNA (siRNA) and chemical inhibitors. The results demonstrated that the entry of both viral forms is dependent on Rab13 and PKA.
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