Mammals rely on an elaborate intracellular trafficking pathway for processing and delivering vitamin B to two client enzymes. CblC (also known as MMACHC) is postulated to receive the cofactor as it enters the cytoplasm and converts varied B derivatives to a common cob(II)alamin intermediate. CblD (or MMADHC) reacts with CblC-bound cob(II)alamin forming an interprotein thiolato-cobalt coordination complex and, by a mechanism that remains to be elucidated, transfers the cofactor to methionine synthase. In the mitochondrion, CblB (also known as MMAB or adenosyltransferase) synthesizes AdoCbl from cob(II)alamin and ATP in the presence of an electron donor. CblA (or MMAA), a GTPase, gates cofactor loading from CblB to methylmalonyl-CoA mutase and off-loading of cob(II)alamin in the reverse direction. This chapter focuses on assays for measuring the activities of the four B chaperones CblA-D.
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http://dx.doi.org/10.1016/bs.mie.2021.12.009 | DOI Listing |
Autophagy
January 2025
Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
The multi-step macroautophagy/autophagy process ends with the cargo-laden autophagosome fusing with the lysosome to deliver the materials to be degraded. The metazoan-specific autophagy factor EPG5 plays a crucial role in this step by enforcing fusion specificity and preventing mistargeting. How EPG5 exerts its critical function and how its deficiency leads to diverse phenotypes of the rare multi-system disorder Vici syndrome are not fully understood.
View Article and Find Full Text PDFASN Neuro
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
We previously identified a role for dAuxilin (dAux), the fly homolog of Cyclin G-associated kinase, in glial autophagy contributing to Parkinson's disease (PD). To further dissect the mechanism, we present evidence here that lack of glial dAux enhanced the phosphorylation of the autophagy-related protein Atg9 at two newly identified threonine residues, T62 and T69. The enhanced Atg9 phosphorylation in the absence of dAux promotes autophagosome formation and Atg9 trafficking to the autophagosomes in glia.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Functionally derivatized analogs of prenyl lipids are valuable tools for the detection and analysis of prenylated proteins. Using a biotinylated analog of geranylgeranyl, we previously identified Ykt6 as a substrate for a novel protein prenyltransferase, termed geranylgeranyltransferase type III (GGTase-III). Ykt6 is an evolutionarily highly conserved SNARE protein that regulates multiple intracellular trafficking pathways, including intra-Golgi trafficking and autophagosome-lysosome fusion.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Sorbonne Université, CNRS, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Paris, France.
Placental malaria is characterized by the massive accumulation and sequestration of infected erythrocytes in the placental intervillous blood spaces, causing severe birth outcomes. The variant surface antigen VAR2CSA is associated with Plasmodium falciparum sequestration in the placenta via its capacity to adhere to chondroitin sulfate A. We have previously shown that the extracellular region of VAR2CSA is phosphorylated on several residues and that the phosphorylation enhances the adhesive properties of CSA-binding infected erythrocytes.
View Article and Find Full Text PDFBBA Adv
December 2024
University of São Paulo, Department of Cell and Developmental Biology, Institute of Biomedical Sciences (ICB), São Paulo, 05508-000, Brazil.
Metastases are the leading cause of cancer-related deaths, and their origin is not fully elucidated. Recently, studies have shown that extracellular vesicles (EVs), particularly small extracellular vesicles (sEV), can disrupt the homeostasis of organs, promoting the development of a secondary tumor. However, the role of sEV in brain endothelium and their association with metastasis related to breast cancer is unknown.
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