Post-Golgi transport for specific membrane domains, also termed polarized transport, is essential for the construction and maintenance of polarized cells. Highly polarized photoreceptors serve as a good model system for studying the mechanisms underlying polarized transport. The Mss4 ortholog, Stratum (Strat), controls basal restriction of basement membrane proteins in follicle cells, and Rab8 acts downstream of Strat. We investigated the function of Strat in fly photoreceptors and found that polarized transport in both the basolateral and the rhabdomere membrane domains was inhibited in -deficient photoreceptors. We also observed 79 and 55% reductions in Rab10 and Rab35 levels, respectively, but no reduction in Rab11 levels in whole-eye homozygous clones of . Moreover, Rab35 was localized in the rhabdomere, and loss of Rab35 resulted in impaired Rh1 transport to the rhabdomere. These results indicate that Strat is essential for the stable expression of Rab10 and Rab35, which regulate basolateral and rhabdomere transport, respectively, in fly photoreceptors.
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http://dx.doi.org/10.1091/mbc.E21-12-0596 | DOI Listing |
Biol Open
August 2022
Department of Anesthesiology and Department of Physiology, Pharmacology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
The Parkinson's-disease-associated LRRK2 kinase phosphorylates multiple Rab GTPases including Rab8 and Rab10, which enhances their binding to RILPL1 and RILPL2. The nascent interaction between phospho-Rab10 and RILPL1 blocks ciliogenesis in vitro and in the intact brain, and interferes with the cohesion of duplicated centrosomes in dividing cells. We show here that regulators of the LRRK2 signaling pathway including vps35 and PPM1H converge upon causing centrosomal deficits.
View Article and Find Full Text PDFMol Biol Cell
September 2022
Program of Life and Environmental Science, Graduate School of Integral Science for Life, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8521, Japan.
Post-Golgi transport for specific membrane domains, also termed polarized transport, is essential for the construction and maintenance of polarized cells. Highly polarized photoreceptors serve as a good model system for studying the mechanisms underlying polarized transport. The Mss4 ortholog, Stratum (Strat), controls basal restriction of basement membrane proteins in follicle cells, and Rab8 acts downstream of Strat.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2022
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Exosomes are membrane vesicles released by various cell types into the extracellular space under different conditions including alcohol exposure. Exosomes are involved in intercellular communication and as mediators of various diseases. Alcohol use causes oxidative stress that promotes exosome secretion.
View Article and Find Full Text PDFBiochem J
January 2021
Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, U.K.
Mutations that increase the protein kinase activity of LRRK2 are one of the most common causes of familial Parkinson's disease. LRRK2 phosphorylates a subset of Rab GTPases within their Switch-II motif, impacting interaction with effectors. We describe and validate a new, multiplexed targeted mass spectrometry assay to quantify endogenous levels of LRRK2-phosphorylated Rab substrates (Rab1, Rab3, Rab8, Rab10, Rab35 and Rab43) as well as total levels of Rabs, LRRK2 and LRRK2-phosphorylated at the Ser910 and Ser935 biomarker sites.
View Article and Find Full Text PDFSci Adv
November 2020
Cell Biology and Gene Expression Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Genetic variation around the LRRK2 gene affects risk of both familial and sporadic Parkinson's disease (PD). However, the biological functions of LRRK2 remain incompletely understood. Here, we report that LRRK2 is recruited to lysosomes after exposure of cells to the lysosome membrane-rupturing agent LLOME.
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