Glycosylphosphatidylinositol-phospholipase C (GPI-PLC) is an enzyme that has been implicated in GPI-dependent protein trafficking and phosphoinositide metabolism in the bloodstream stage of African trypanosomes. However, despite the fact that it is associated with the cytoplasmic face of internal organellar compartments, its role in general membrane trafficking has not been investigated. Using a GPI-PLC null cell line, we determine the effect of GPI-PLC deficiency on these processes. Biosynthetic trafficking of lysosomal cargo, soluble cathepsin L and membrane bound p67, are unaffected. Likewise, secretory transport, recycling and ultimate lysosomal turnover of the GPI-anchored and transmembrane glycoproteins, transferrin receptor and invariant surface glycoprotein 65, respectively, were unaffected. A significant decrease in the endocytic uptake of transferrin was observed, confirming a prior report, but ultimate delivery to the lysosome was unimpacted. These results contribute to our understanding of the roles of this enigmatic enzyme in trypanosome cell biology.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.molbiopara.2021.111409 | DOI Listing |
Alzheimers Dement
December 2024
Acumen Pharmaceuticals, Charlottesville, VA, USA.
Background: Sabirnetug (ACU193) is a humanized IgG2 antibody targeting soluble, synaptotoxic amyloid β oligomers (AβOs). AβOs accumulate in Alzheimer's disease (AD) and induce pre- and post-synaptic changes, resulting in dendritic spine loss, neuronal degeneration, and release of synaptic proteins into the CSF. Recently, we reported that three administrations of sabirnetug in an early AD population (INTERCEPT-AD Phase 1 study, NCT04931459) significantly lowered CSF levels of the post-synaptic protein neurogranin as well as pTau181.
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 PDFBackground: Genetic studies have established that loss of function SORL1 gene variants are associated with Alzheimer's disease (AD). SORL1 encodes an endosomal trafficking receptor, SORLA, which regulates endosomal protein recycling through its interaction with the retromer core complex (consisting of VPS26, VPS35 and VPS29). Deficits in the levels and function of the SORLA-retromer complex are thought to underlie AD.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics.
View Article and Find Full Text PDFSci Rep
January 2025
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
GABA receptors mediate prolonged inhibition in the brain and are important for keeping neuronal excitation and inhibition in a healthy balance. However, under excitotoxic/ischemic conditions, GABA receptors are downregulated by dysregulated endocytic trafficking and can no longer counteract the severely enhanced excitation, eventually triggering neuronal death. Recently, we developed interfering peptides targeting protein-protein interactions involved in downregulating the receptors.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!