Rab7a in Endocytosis and Signaling

BasuRay, Soumik; Agola, Jacob O.; Jim, Patricia A.; Seaman, Matthew N.; Wandinger‐Ness, Angela

doi:10.1007/978-3-319-67199-4_623

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…This, in turn, results in increased association of the retromer CSC (a Rab7a effector), with Rab7a and most likely accounts for the elevated levels of endosomally localised retromer CSC proteins. Increased active Rab7a would be predicted to also lead to changes in lysosome function and/or morphology as Rab7a is a key regulator of lysosomes ( Basuray et al, 2012 ; Guerra and Bucci, 2016 ). We did observe changes in the morphology of lysosomes (using the protein Lamp1 as a marker) after TBC1D5 knockdown in line with changes elicited by knockdown of Rab7a itself (see …”

Section: Discussionmentioning

confidence: 99%

Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex

Seaman

Mukadam

Breusegem

2018

Journal of Cell Science

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The retromer complex is a vital component of the endosomal protein sorting machinery necessary for sorting into both the endosome-to-Golgi retrieval pathway and also the endosome-to-cell-surface recycling pathway. Retromer mediates cargo selection through a trimeric complex comprising VPS35, VPS29 and VPS26, which is recruited to endosomes by binding to Rab7a and Snx3. Retromer function is linked to two distinct neurodegenerative diseases, Parkinson's disease and Alzheimer's disease and modulating retromer function has been proposed as an avenue to explore for a putative therapy in these conditions. We hypothesised that activating Rab7a to promote the recruitment of retromer to endosomes could positively modulate its activity. Here, we show that inhibition of the GTPase activating protein TBC1D5 can enhance Rab7a activation and lead to a gain of function for retromer.

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Section: Discussionmentioning

confidence: 99%

Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex

Seaman

Mukadam

Breusegem

2018

Journal of Cell Science

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“…Rab GTPases are amongst the fundamental proteins of a cell regulating important cellular mechanisms like membrane trafficking (Hutagalung & Novick, 2011). A number of comprehensive studies summarizing the molecular, physiological and pathological aspects of vesicle transport system link trafficking proteins dysfunction with human diseases such as carcinoma, neurodegenerative disorders, charcot-marie-tooth type B and diabetes (BasuRay et al, 2013;Mafakheri et al, 2018;Millecamps & Julien, 2013;Tzeng & Wang, 2016). Interestingly, the involvement of Rab GTPases in underlying mechanisms implicating IBD is still not well understood.…”

Section: Discussionmentioning

confidence: 99%

Rab7 dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis

Gaur¹,

Yesheswini²,

Srivastava

et al. 2023

Preprint

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Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier coupled with microbial dysbiosis has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease Chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7 dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.

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“…In fungi, the number of Ypt family is stable from 7 to 12 Ypts, each of which may be responsible for a particular stage of the membrane transport pathway (Pereira-Leal, 2008 ; Li and Marlin, 2015 ). Among them, Ypt7 is proved as a key regulator of the material movement and transformation among cellular compartments through vacuolar biogenesis and fusion (Ohsumi et al, 2002 ; Kashiwazaki et al, 2009 ; Balderhaar et al, 2010 ; Wickner, 2010 ), and the Ypt7-mediated vacuolar fission and fusion are proved to be essential for maintaining stabilities of the cytosolic pH and osmolarity, and storing and transferring intermediary metabolites like mammalian lysosomes and plant vacuoles (Richards et al, 2010 ; de Marcos Lousa and Denecke, 2016 ; BasuRay et al, 2018 ), while some investigations have also showed that Ypt7 can influence fungal development and secondary metabolism. For example, the ypt 7 gene deletion or overexpression can lead to the variances of conidiogenesis and metabolism in fungi (Chanda et al, 2009a ; Xu et al, 2012 ; Li et al, 2015 ; Liu et al, 2015 ; Zheng et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Analysis of the Small GTPases Ypt7 Involved in the Regulation of Fungal Development and Secondary Metabolism in Monascus ruber M7

et al. 2019

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Ypts (yeast protein transports),also called as ras-associated binding GTPases (Rab), are the largest group of the small GTPases family, which have been extensively studied in model eukaryotic cells and play a pivotal role in membane trafficking, while this study showed potential regulation role of Ypts in fungi. One of Ypts, Ypt7 may be involved in fungal development and secondary metabolism, but the exact mechanism still exists a controversy. In current study, the functions of a Monascus ypt7 homologous gene (mrypt7) from Monascus ruber M7 was investigated by combination of gene-deletion (Δmrypt7), overexpression (M7::PtrpC-mrypt7) and transcriptome analysis. Results showed that the radial growth rate of Δmrypt7 was significantly slower than M. ruber M7, little conidia and ascospores can be observed in Δmrypt7, but the yield of intracellular secondary metabolites was dramatically increased. Simultaneously, the mrypt7 overexpression strain possessed similar capacity for sporulation and secondary metabolism observed in M. ruber M7. Transcriptome results further illustrated that mrypt7 could coordinate with numerous genes involved in the vegetative growth, conidiogenesis, secondary metabolism biosynthesis and transportation of M. ruber M7. Combined with the similar effect of Ypt7 homologs on other fungi, we propose that Ypt7 works more like a global regulatory factor in fungi. To our knowledge, it is the first time to investigate Ypt7 functions in Monascus. It could also improve the understanding of Ypt7 functions in fungi.

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Rab7a in Endocytosis and Signaling

Cited by 4 publications

References 34 publications

Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex

Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex

Rab7 dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis

A Comprehensive Analysis of the Small GTPases Ypt7 Involved in the Regulation of Fungal Development and Secondary Metabolism in Monascus ruber M7

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