Raft endocytosis of autocrine motility factor regulates mitochondrial dynamics via rac1 signaling and the gp78 ubiquitin ligase

Shankar, Jata; Kojic, Liliana D.; St-Pierre, Pascal; Wang, Peter T. C.; Fu, Min; Joshi, Bharat; Nabi, Ivan R.

doi:10.1242/jcs.120162

Cited by 23 publications

(19 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stable HT-1080 clones expressing control shCtl and Gp78-targeted shGp78 shRNAs (corresponding to sh6 Gp78 shRNA in Shankar et al, 2013) in doxycyclin-inducible pTRIPZ plasmid were maintained in medium containing 2 mg/ml puromycin and 1 mg/ml doxycyclin to induce Gp78 knockdown. For AMF treatment, cells were serum starved overnight and incubated with fresh medium containing 24 µg/ml AMF.…”

Section: Cell Culture Constructs and Treatmentsmentioning

confidence: 99%

“…The ER is associated with mitochondrial fission sites (Friedman et al, 2011) and Gp78 ubiquitin ligase activity targets the mitochondrial fusion proteins, mitofusin 1 (Mfn1) and Mfn2, for degradation inducing mitochondrial fission and, upon mitochondrial depolarization, mitophagy . Dynamin-and Rac1-PI3K-dependent raft internalization of AMF to the Gp78-positive ER prevents Gp78 degradation of the mitofusins and reverses Gp78-dependent mitochondrial fission (Kojic et al, 2007;Le et al, 2002;Shankar et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct mechanisms controlling rough and smooth endoplasmic reticulum-mitochondria contacts

Wang

Garcin

et al. 2015

Journal of Cell Science

Self Cite

102

View full text Add to dashboard Cite

Gp78 (also known as AMFR), an endoplasmic-reticulum (ER)-associated protein degradation (ERAD) E3 ubiquitin ligase, localizes to mitochondria-associated ER and targets the mitofusin (Mfn1 and Mfn2) mitochondrial fusion proteins for degradation. Gp78 is also the cell surface receptor for autocrine motility factor (AMF), which prevents Gp78-dependent mitofusin degradation. Gp78 ubiquitin ligase activity promotes ER-mitochondria association and ER-mitochondria Ca 2+ coupling, processes that are reversed by AMF. Electron microscopy of HT-1080 fibrosarcoma cancer cells identified both smooth ER (SER; ∼8 nm) and wider (∼50-60 nm) rough ER (RER)-mitochondria contacts. Both short hairpin RNA (shRNA)-mediated knockdown of Gp78 (shGp78) and AMF treatment selectively reduced the extent of RER-mitochondria contacts without impacting on SER-mitochondria contacts. Concomitant small interfering RNA (siRNA)-mediated knockdown of Mfn1 increased SER-mitochondria contacts in both control and shGp78 cells, whereas knockdown of Mfn2 increased RER-mitochondria contacts selectively in shGp78 HT-1080 cells. The mitofusins therefore inhibit ER-mitochondria interaction. Regulation of close SER-mitochondria contacts by Mfn1 and of RER-mitochondria contacts by AMFsensitive Gp78-mediated degradation of Mfn2 define new mechanisms that regulate ER-mitochondria interactions.

show abstract

Section: Cell Culture Constructs and Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct mechanisms controlling rough and smooth endoplasmic reticulum-mitochondria contacts

Wang

Garcin

et al. 2015

Journal of Cell Science

Self Cite

102

View full text Add to dashboard Cite

show abstract

“…; Shankar et al . ), and is reported to protect against ER stress and apoptosis by regulation of ER calcium release (Fu et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…neuroleukin; autocrine motility factor) is a pleiotropic protein performing different functions inside the cell and in the extracellular space. In the cytoplasm, GPI catalyzes the second step in glycolysis, regulates gp78-dependent mitochondrial fission and mitophagy Shankar et al 2013), and is reported to protect against ER stress and apoptosis by regulation of ER calcium release (Fu et al 2011). Outside the cell, GPI acts as a neurotropic factor for spinal and sensory neurons, contributing to maintenance of neuronal integrity (Haga et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Metabolic clues to salubrious longevity in the brain of the longest‐lived rodent: the naked mole‐rat

Triplett

Swomley

Kirk

et al. 2015

Journal of Neurochemistry

View full text Add to dashboard Cite

Naked mole-rats (NMRs) are the oldest-living rodent species. Living underground in a thermally stable ecological niche, NMRs have evolved certain exceptional traits, resulting in sustained health spans, negligible cognitive decline, and a pronounced resistance to age-related disease. Uncovering insights into mechanisms underlying these extraordinary traits involved in successful aging may conceivably provide crucial clues to extend the human life span and health span. One of the most fundamental processes inside the cell is the production of ATP, which is an essential fuel in driving all other energy-requiring cellular activities. Not surprisingly, a prominent hallmark in age-related diseases, such as neurodegeneration and cancer, is the impairment and dysregulation of metabolic pathways. Using a two-dimensional polyacrylamide gel electrophoresis proteomics approach, alterations in expression and phosphorylation levels of metabolic proteins in the brainsofNMRs,aged2-24 years,wereevaluatedinanage-dependent manner. We identified 13 proteins with altered levels and/or phosphorylation states that play key roles in various metabolic pathways including glycolysis, b-oxidation, the malate-aspartate shuttle, the Tricarboxylic Acid Cycle (TCA) cycle, the electron transport chain, NADPH production, as well as the production of glutamate. New insights into potential pathways involved in metabolic aspects of successful aging have been obtained by the identification of key proteins through which the NMR brain responds and adapts to the aging process and how the NMR brain adapted to resist age-related degeneration.

show abstract

“…It was recently shown that some bacterial toxins of the Clostridium family can hijack the IL2-R pathway for cell intoxication (41). The AMF is endocytosed by a pathway that is regulated in a similar manner except for the sensitivity to RhoA (42). It is not known whether IFNAR and IFNGR can take the IL2-R endocytic route.…”

Section: Clathrin-independent Endocytosismentioning

confidence: 99%

Interferon Gamma Receptor: The Beginning of the Journey

Blouin¹,

Lamaze²

2013

Front. Immunol.

View full text Add to dashboard Cite

Our view of endocytosis and membrane trafficking of transmembrane receptors has dramatically changed over the last 20 years. Several new endocytic routes have been discovered and mechanistically characterized in mammalian cells. Long considered as a passive means to terminate signaling through down-regulation of the number of activated receptors at the plasma membrane, it is now established that receptor endocytosis and endosomal sorting can be directly linked to the regulation of intracellular signaling pathways. The functional links between membrane trafficking of interferon receptors and JAK/STAT signaling have recently begun to be unraveled. These studies raise the exciting possibility that a certain level of signal specificity can be achieved through endocytosis and selective localization of the activated complexes within cellular membranes. The ongoing development of high-resolution cell imaging techniques with better spatial and temporal resolution gives new means of deciphering the inherent complexity of membrane trafficking and signaling. This should help to better comprehend the molecular mechanisms by which endocytosis and endosomal sorting of interferon receptors can orchestrate signaling selectivity within the JAK/STAT pathway that can be activated by as many as 60 different cytokines, growth factors, and hormones.

show abstract

Raft endocytosis of autocrine motility factor regulates mitochondrial dynamics via rac1 signaling and the gp78 ubiquitin ligase

Cited by 23 publications

References 54 publications

Distinct mechanisms controlling rough and smooth endoplasmic reticulum-mitochondria contacts

Distinct mechanisms controlling rough and smooth endoplasmic reticulum-mitochondria contacts

Metabolic clues to salubrious longevity in the brain of the longest‐lived rodent: the naked mole‐rat

Interferon Gamma Receptor: The Beginning of the Journey

Contact Info

Product

Resources

About