Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation

Russo, Ashley J.; Mathiowetz, Alyssa J.; Hong, Steven; Welch, Matthew D.; Campellone, Kenneth

doi:10.1091/mbc.e15-07-0508

Cited by 32 publications

(45 citation statements)

References 52 publications

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“…Rab1, in particular, has been implicated in regulating actin assembly through interaction with WHAMM [89]. In mammalian cells, the number of autophagosomes increases with overexpression of Rab1, and a constitutively active form of Rab1 strongly colocalizes with LC3-II after induction of macroautophagy [90].…”

Section: Gtpase Signaling and Autophagymentioning

confidence: 99%

“…In mammalian cells, the number of autophagosomes increases with overexpression of Rab1, and a constitutively active form of Rab1 strongly colocalizes with LC3-II after induction of macroautophagy [90]. Rab1 expression also promotes the accumulation of WHAMM on the ER, which leads to increased membrane tubulation [89]. This effect could be due to inhibition of the Arp2/3 complex, since Rab1 inhibits the WHAMM-dependent activation of the Arp2/3 complex in vitro [89] and Arp2/3 complex inhibition by CK-666 also leads to an increase in WHAMM-coated tubules [7].…”

Section: Gtpase Signaling and Autophagymentioning

confidence: 99%

“…Rab1 expression also promotes the accumulation of WHAMM on the ER, which leads to increased membrane tubulation [89]. This effect could be due to inhibition of the Arp2/3 complex, since Rab1 inhibits the WHAMM-dependent activation of the Arp2/3 complex in vitro [89] and Arp2/3 complex inhibition by CK-666 also leads to an increase in WHAMM-coated tubules [7]. …”

Section: Gtpase Signaling and Autophagymentioning

confidence: 99%

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The Cytoskeleton–Autophagy Connection

2017

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Summary Actin cytoskeleton dynamics plays vital roles in most forms of intracellular trafficking by promoting the biogenesis and transport of vesicular cargoes. Mounting evidence indicates that actin dynamics and membrane-cytoskeleton scaffolds also play essential roles in macroautophagy, the process by which cellular waste is isolated inside specialized vesicles called autophagosomes for recycling and degradation. Thus, branched-actin polymerization is necessary for the biogenesis of autophagosomes from the endoplasmic reticulum (ER) membrane. Actomyosin-based transport is then used to feed the growing phagophore with pre-selected cargoes and debris derived from different membranous organelles inside the cell. Mature autophagosomes then detach from the ER membrane by an unknown mechanism, and are transported and fused with lysosomes, endosomes and multi-vesicular bodies through mechanisms that involve actin- and microtubule-based motility, cytoskeleton-membrane scaffolds and signaling proteins. In this minireview, we highlight the considerable progress made recently towards understanding the diverse roles of the cytoskeleton in autophagy.

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Section: Gtpase Signaling and Autophagymentioning

confidence: 99%

Section: Gtpase Signaling and Autophagymentioning

confidence: 99%

Section: Gtpase Signaling and Autophagymentioning

confidence: 99%

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The Cytoskeleton–Autophagy Connection

2017

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“…WHAMM has been found to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) where it regulates vesicle transport (Campellone et al, 2008). Rab1 (also known as Rab1a) has been shown to inhibit WHAMM-mediated actin assembly in vitro and regulate WHAMM membrane recruitment through an interaction with the WMD (Russo et al, 2016). More recent studies have shown that RhoD interacts with WHAMM to regulate Golgi structure and the transport of cargo to the plasma membrane (Blom et al, 2015;Gad et al, 2012).…”

Section: Regulation and Cytoplasmic Functions Of Whamm Jmy And Wash mentioning

confidence: 99%

Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

158

172

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Proteins of the Wiskott–Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network. Recent studies have also identified roles for WASP family members in promoting actin dynamics at the centrosome, influencing nuclear shape and membrane remodeling events leading to the generation of autophagosomes. Interestingly, several WASP family members have also been observed in the nucleus where they directly influence gene expression by serving as molecular platforms for the assembly of epigenetic and transcriptional machinery. In this Cell Science at a Glance article and accompanying poster, we provide an update on the subcellular roles of WHAMM, JMY and WASH (also known as WASHC1), as well as their mechanisms of regulation and emerging functions within the cell.

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“…WASH is also part of a large regulatory complex analogous to that of the WAVEs [29, 30, 67]. It is not yet known if WHAMM or JMY exist in stable multi-subunit complexes, although WHAMM’s nucleation-promoting activity can be suppressed upon binding microtubules or the small G-protein Rab1 [33, 68], and JMY-mediated actin assembly can be inhibited by the protein Strap [69].…”

Section: Introductionmentioning

confidence: 99%

WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility

Kabrawala

Zimmer

Campellone

2020

Preprint

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17Cell motility is governed by cooperation between the Arp2/3 complex and nucleation factors 18 from the Wiskott-Aldrich Syndrome Protein (WASP) family, which together assemble actin 19 filament networks to drive membrane protrusion. Here we identify WHIMP (WAVE Homology In 20Membrane Protrusions) as a new member of the WASP family. The Whimp gene is encoded on 21 the X-chromosome of multiple animals, including mice. Murine WHIMP promotes Arp2/3-22 dependent actin assembly, but is less potent than other nucleation factors. Nevertheless, 23 WHIMP-mediated Arp2/3 activation enhances both plasma membrane ruffling and wound 24 healing migration, whereas WHIMP depletion impairs protrusion and slows motility. WHIMP 25 expression also increases Src-family kinase activity, and WHIMP-induced ruffles contain the 26 additional nucleation factors WAVE1, WAVE2, and N-WASP, but not JMY or WASH. Perturbing 27 the function of Src-family kinases, WAVE proteins, or Arp2/3 complex inhibits WHIMP-driven 28 ruffling. These results suggest that WHIMP-mediated actin assembly plays a direct role in 29 membrane protrusion, but also results in feedback control of tyrosine kinase signaling to 30 modulate the activation of multiple WASP-family proteins. 31 32 33 3 AUTHOR SUMMARY 34The actin cytoskeleton is a collection of protein polymers that assemble and disassemble within 35 cells at specific times and locations. Sophisticated cytoskeletal regulators called nucleation 36 factors ensure that actin polymerizes when and where it is needed, and most nucleation factors 37 are members of the Wiskott-Aldrich Syndrome Protein (WASP) family. Several of the 8 known 38WASP-family proteins function in cell motility, but how the different factors collaborate with one 39 another is not well understood. In this study, we identified WHIMP, a new WASP-family 40 member which is encoded on the X chromosome of a variety of animals. In mouse cells, 41 WHIMP enhances cell motility by assembling actin filaments that push the cell membrane 42 forward. Unexpectedly, WHIMP also activates tyrosine kinase enzymes, proteins that stimulate 43 multiple WASP-family members during motility. Our results open new avenues of research into 44 how nucleation factors cooperate during movement and how the molecular activities that 45 underlie motility differ in distinct cell types and organisms. 46 47 48 the recruitment and activation of a 7-subunit macromolecule named the Arp2/3 complex [2], 52 which acts in concert with binding partners called nucleation-promoting factors [3]. Many such 53 factors are members of the Wiskott-Aldrich Syndrome Protein (WASP) family, and are integral in 54 activating the complex at different cellular locations [4]. Most WASP-family proteins promote 55 actin assembly during membrane protrusion and cell motility [5], but how the different factors 56 collaborate during these processes is not well understood. 57 WASP-family members are defined by the presence of a WH2-Connector-Acidic (WCA) 58 domain in which one or more WH2 motifs bind actin monome...

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Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation

Cited by 32 publications

References 52 publications

The Cytoskeleton–Autophagy Connection

The Cytoskeleton–Autophagy Connection

Cellular functions of WASP family proteins at a glance

WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility

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