Eeyarestatin 24 impairs SecYEG‐dependent protein trafficking and inhibits growth of clinically relevant pathogens

Ubiquitylation is a key regulator of protein trafficking, and much about the functions of ubiquitin ligases, which add ubiquitin to substrates in this regulation, has recently come to light. However, a clear understanding of ubiquitin-dependent protein localization cannot be achieved without knowledge of the role of deubiquitylating enzymes (DUBs). DUBs, by definition, function downstream in ubiquitin pathways and, as such, have the potential to be the final editors of protein ubiquitylation status, thus determining substrate fate. This paper assimilates the current evidence concerning the substrates and activities of DUBs that regulate protein trafficking.

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Loss of CHIP Expression Perturbs Glucose Homeostasis and Leads to Type II Diabetes through Defects in Microtubule Polymerization and Glucose Transporter Localization

10.1101/166389 ◽

2017 ◽

Cited By ~ 1

Author(s):

Holly McDonough ◽

Kaitlin C. Lenhart ◽

Sarah M. Ronnebaum ◽

Chunlian Zhang ◽

Jie An ◽

...

Keyword(s):

Glucose Homeostasis ◽

Protein Trafficking ◽

Type Ii Diabetes ◽

Glucose Transporter ◽

Protein A ◽

Whole Body ◽

Type Ii ◽

Interacting Protein ◽

Microtubule Polymerization ◽

Dependent Protein

ABSTRACTRecent evidence has implicated CHIP (carboxyl terminus of Hsc/Hsp70-interacting protein), a co-chaperone and ubiquitin ligase, in the functional support of several metabolism-related proteins, including AMPK and SirT6. In addition to previously reported aging and stress intolerance phenotypes, we find that CHIP -/- mice also demonstrate a Type II diabetes-like phenotype, including poor glucose tolerance, decreased sensitivity to insulin, and decreased insulin-stimulated glucose uptake in isolated skeletal muscle, characteristic of insulin resistance. In CHIP-deficient cells, glucose stimulation fails to induce translocation of Glut4 to the plasma membrane. This impairment in Glut4 translocation in CHIP-deficient cells is accompanied by decreased tubulin polymerization associated with decreased phosphorylation of stathmin, a microtubule-associated protein required for polymerization-dependent protein trafficking within the cell. Together, these data describe a novel role for CHIP in regulating microtubule polymerization that assists in glucose transporter translocation, promoting whole-body glucose homeostasis and sensitivity to insulin.

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AtCAP2 is crucial for lytic vacuole biogenesis during germination by positively regulating vacuolar protein trafficking

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1717204115 ◽

2018 ◽

Vol 115 (7) ◽

pp. E1675-E1683 ◽

Cited By ~ 5

Author(s):

Yun Kwon ◽

Jinbo Shen ◽

Myoung Hui Lee ◽

Kyoung Rok Geem ◽

Liwen Jiang ◽

...

Keyword(s):

Plant Development ◽

Protein Trafficking ◽

Adaptor Protein ◽

Mature Stage ◽

Loss Of Function ◽

Calcium Dependent ◽

Dependent Protein ◽

Lytic Vacuole ◽

Vacuolar Protein ◽

Vacuole Biogenesis

Protein trafficking is a fundamental mechanism of subcellular organization and contributes to organellar biogenesis. AtCAP2 is an Arabidopsis homolog of the Mesembryanthemum crystallinum calcium-dependent protein kinase 1 adaptor protein 2 (McCAP2), a member of the syntaxin superfamily. Here, we show that AtCAP2 plays an important role in the conversion to the lytic vacuole (LV) during early plant development. The AtCAP2 loss-of-function mutant atcap2-1 displayed delays in protein storage vacuole (PSV) protein degradation, PSV fusion, LV acidification, and biosynthesis of several vacuolar proteins during germination. At the mature stage, atcap2-1 plants accumulated vacuolar proteins in the prevacuolar compartment (PVC) instead of the LV. In wild-type plants, AtCAP2 localizes to the PVC as a peripheral membrane protein and in the PVC compartment recruits glyceraldehyde-3-phosphate dehydrogenase C2 (GAPC2) to the PVC. We propose that AtCAP2 contributes to LV biogenesis during early plant development by supporting the trafficking of specific proteins involved in the PSV-to-LV transition and LV acidification during early stages of plant development.

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Vac14 Controls PtdIns(3,5) P 2 Synthesis and Fab1-Dependent Protein Trafficking to the Multivesicular Body

Current Biology ◽

10.1016/s0960-9822(02)00891-6 ◽

2002 ◽

Vol 12 (11) ◽

pp. 885-893 ◽

Cited By ~ 94

Author(s):

Stephen K. Dove ◽

Robert K. McEwen ◽

Andrew Mayes ◽

David C. Hughes ◽

Jean D. Beggs ◽

...

Keyword(s):

Protein Trafficking ◽

Multivesicular Body ◽

Dependent Protein

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CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cells

Cancer Letters ◽

10.1016/j.canlet.2011.02.024 ◽

2011 ◽

Vol 306 (1) ◽

pp. 43-51 ◽

Cited By ~ 11

Author(s):

Massod Rahimi ◽

Theodore A. Toth ◽

Careen K. Tang

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

P38 Mapk ◽

Protein Trafficking ◽

Breast Cancer Cells ◽

Dependent Protein

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The Vaccinia Virus F13L YPPL Motif Is Required for Efficient Release of Extracellular Enveloped Virus

Journal of Virology ◽

10.1128/jvi.00034-07 ◽

2007 ◽

Vol 81 (13) ◽

pp. 7310-7315 ◽

Cited By ~ 32

Author(s):

Kady M. Honeychurch ◽

Guang Yang ◽

Robert Jordan ◽

Dennis E. Hruby

Keyword(s):

Rna Interference ◽

Vaccinia Virus ◽

Protein Trafficking ◽

Host Proteins ◽

Recombinant Viruses ◽

Enveloped Virus ◽

Leucine Residue ◽

Virion Production ◽

Pcr Products ◽

Dependent Protein

ABSTRACT The Tyr-X-X-Leu (YxxL) motif of the vaccinia virus F13L protein was examined for late (L) domain activity. The ability of an F13L deletion virus to form plaques was restored by PCR products containing single alanine substitutions within the motif and a YAAL construct but not by constructs lacking both the Y and L residues. Recombinant viruses possessing alanine substitutions in place of the tyrosine or the leucine residue in the YxxL motif demonstrated small, asymmetrical plaques. RNA interference-dependent depletion of Alix and TSG101 (host proteins involved in L domain-dependent protein trafficking) diminished extracellular enveloped virion production to various degrees, suggesting that the YxxL motif is a genuine L domain.

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A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment

Neuronal Signaling ◽

10.1042/ns20210005 ◽

2021 ◽

Vol 5 (4) ◽

Author(s):

Andrey A. Petropavlovskiy ◽

Jordan A. Kogut ◽

Arshia Leekha ◽

Charlotte A. Townsend ◽

Shaun S. Sanders

Keyword(s):

Protein Trafficking ◽

Lipid Membranes ◽

Initial Segment ◽

Protein Targeting ◽

Neurological Diseases ◽

Axon Initial Segment ◽

Neuronal Proteins ◽

Dependent Protein ◽

Specific Proteins ◽

And Function

Abstract In neurons, the axon and axon initial segment (AIS) are critical structures for action potential initiation and propagation. Their formation and function rely on tight compartmentalisation, a process where specific proteins are trafficked to and retained at distinct subcellular locations. One mechanism which regulates protein trafficking and association with lipid membranes is the modification of protein cysteine residues with the 16-carbon palmitic acid, known as S-acylation or palmitoylation. Palmitoylation, akin to phosphorylation, is reversible, with palmitate cycling being mediated by substrate-specific enzymes. Palmitoylation is well-known to be highly prevalent among neuronal proteins and is well studied in the context of the synapse. Comparatively, how palmitoylation regulates trafficking and clustering of axonal and AIS proteins remains less understood. This review provides an overview of the current understanding of the biochemical regulation of palmitoylation, its involvement in various neurological diseases, and the most up-to-date perspective on axonal palmitoylation. Through a palmitoylation analysis of the AIS proteome, we also report that an overwhelming proportion of AIS proteins are likely palmitoylated. Overall, our review and analysis confirm a central role for palmitoylation in the formation and function of the axon and AIS and provide a resource for further exploration of palmitoylation-dependent protein targeting to and function at the AIS.

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