Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts

Balasubramanian, Nagaraj; Scott, David W.; Castle, J. David; Casanova, James E.; Schwartz, Martin A.

doi:10.1038/ncb1657

Cited by 199 publications

(202 citation statements)

References 50 publications

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“…However, replating onto fibronectin-coated substrates triggers the rapid activation of Arf6, the redistribution of internalized rafts to the plasma membrane, and a corresponding activation of Rac as the cells spread. Knockdown of Arf6 leads to the selective retention of raft components in recycling endosomes, a dramatic inhibition of adhesion-induced Rac activation, and impaired cell spreading [32]. These findings suggest that, in addition to its regulation of phospholipid-modifying enzymes and its interaction with Rac GEFs, Arf6 can further modulate Rac activity by controlling the availability of lipid raft components (Figure 3c).…”

Section: The Rac Translocation Modelmentioning

confidence: 90%

“…Conversely, activation of endogenous Arf6 by expression of the Arf GEF ARNO (Arf nucleotide-binding site opener) was found to trigger the activation of Rac, extension of lamellipodia and the onset of migration in normally stationary epithelial cells (Figure 2) [31]. Subsequent studies have confirmed that Arf6 activation is coupled to Rac activation in several settings, including integrin ligation [32,33] or stimulation of cells with vascular endothelial growth factor (VEGF) [34], platelet-derived growth factor (PDGF) [35] or angiotensin II [36].…”

Section: Crosstalk Between Arf6 and Racmentioning

confidence: 96%

“…Therefore, Arf6 could modulate Rac activity by controlling the availability of the necessary lipids at the plasma membrane. Although some of the components of CEMMs (notably PtdIns (4,5)P 2 ) are undoubtedly synthesized locally, recent findings suggest that the recycling of internalized rafts from endosomes also requires active Arf6, and that this has an important role in the attachment and spreading of anchorage-dependent cells [32]. Detachment of cells from the substratum induces the quantitative internalization of lipid raft components from the cell surface, and their accumulation in perinuclear recycling endosomes.…”

Section: The Rac Translocation Modelmentioning

confidence: 99%

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Regulation of actin cytoskeleton dynamics by Arf-family GTPases

Myers

Casanova

2008

Trends in Cell Biology

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167

139

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Small GTPases of the Arf family are best known for their role in vesicular transport, wherein they nucleate the assembly of coat proteins at sites of carrier vesicle formation. However, accumulating evidence indicates that the Arfs are also important regulators of actin cytoskeleton dynamics and are involved in a variety of actin-based processes, including cell adhesion, migration and neurite outgrowth. The mechanisms of this regulation are remarkably diverse, ranging from the integration of vesicular transport with cytoskeleton assembly to the direct regulation of Rho-family GTPase function. Here, we review recent progress in our understanding of how Arfs and their interacting proteins function to integrate membrane and cytoskeletal dynamics.

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Section: The Rac Translocation Modelmentioning

confidence: 90%

Section: Crosstalk Between Arf6 and Racmentioning

confidence: 96%

Section: The Rac Translocation Modelmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of actin cytoskeleton dynamics by Arf-family GTPases

Myers

Casanova

2008

Trends in Cell Biology

Self Cite

167

139

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“…A major reason is that the cell/neuron may use the constitutive or stimulated ARF6 routes to control directly or indirectly the steady-state levels of cell surface receptors important for signaling, as described, for instance, for the EGF receptor (48,49), migration, or antigen presentation (50)(51)(52). Similarly, the ARF6 route likely indirectly controls APP processing by modulating BACE1 trafficking in neurons.…”

Section: Discussionmentioning

confidence: 99%

ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1

Sannerud

Declerck²,

Perić³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

217

232

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Amyloid β (Aβ) peptides, the primary constituents of senile plaques and a hallmark in Alzheimer's disease pathology, are generated through the sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. The early endosome is thought to represent a major compartment for APP processing; however, the mechanisms of how BACE1 encounters APP are largely unknown. In contrast to APP internalization, which is clathrin-dependent, we demonstrate that BACE1 is sorted to early endosomes via a route controlled by the small GTPase ADP ribosylation factor 6 (ARF6). Altering ARF6 levels or its activity affects endosomal sorting of BACE1, and consequently results in altered APP processing and Aβ production. Furthermore, sorting of newly internalized BACE1 from ARF6-positive towards RAB GTPase 5 (RAB5)-positive early endosomes depends on its carboxyterminal short acidic cluster-dileucine motif. This ARF6-mediated sorting of BACE1 is confined to the somatodendritic compartment of polarized neurons in agreement with Aβ peptides being primarily secreted from here. These results demonstrate a spatial separation between APP and BACE1 during surface-toendosome transport, suggesting subcellular trafficking as a regulatory mechanism for this proteolytic processing step. It thereby provides a novel avenue to interfere with Aβ production through a selective modulation of the distinct endosomal transport routes used by BACE1 or APP.

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“…It is possible that the effect of reggie-1 downregulation on Rac1 activation results from abnormal vesicle transport which seems to be normally governed by reggie and Rab11a. This implies that the delivery of Rac1 to specific regions in the cell occurs through its transport at vesicles in HeLa cells (Palamidessi et al, 2008).This affects the phosphoinositide composition of the transport vesicles and increases the preference of Rac1 for lipid rafts (Balasubramanian et al, 2007), which are the microdomains favored by reggies. Rac1 and Rab11 have been shown to interact genetically in Drosophila (Assaker et al, 2010).…”

Section: Influence Of Reggie On Fak Rac1 and Rab11 Activationmentioning

confidence: 99%

Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a

Hülsbusch

Solis

Katanaev

et al. 2015

European Journal of Cell Biology

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a b s t r a c tReggies/flotillins are implicated in trafficking of membrane proteins to their target sites and in the regulation of the Rab11a-dependent targeted recycling of E-cadherin to adherens junctions (AJs). Here we demonstrate a function of reggies in focal adhesion (FA) formation and ␣5-and ␤1-integrin recycling to FAs. Downregulation of reggie-1 in HeLa and A431 cells by siRNA and shRNA increased the number of FAs, impaired their distribution and modified FA turnover. This was coupled to enhanced focal adhesion kinase (FAK) and Rac1 signaling and gain in plasma membrane motility. Wild type and constitutively-active (CA) Rab11a rescued the phenotype (normal number of FAs) whereas dominant-negative (DN) Rab11a mimicked the loss-of-reggie phenotype in control cells. That reggie-1 affects integrin trafficking emerged from the faster loss of internalized antibody-labeled ␤1-integrin in reggie-deficient cells. Moreover, live imaging using TIRF microscopy revealed vesicles containing reggie-1 and ␣5-or ␤1-integrin, trafficking close to the substrate-near membrane and making kiss-and-run contacts with FAs. Thus, reggie-1 in interaction with Rab11a controls Rac1 and FAK activation and coordinates the targeted recycling of ␣5-and ␤1-integrins to FAs to regulate FA formation and membrane dynamics.

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Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts

Cited by 199 publications

References 50 publications

Regulation of actin cytoskeleton dynamics by Arf-family GTPases

Regulation of actin cytoskeleton dynamics by Arf-family GTPases

ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1

Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a

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