A FAM21-Containing WASH Complex Regulates Retromer-Dependent Sorting

Gomez, Timothy S.; Billadeau, Daniel D.

doi:10.1016/j.devcel.2009.09.009

Cited by 476 publications

(876 citation statements)

References 40 publications

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“…WASH localizes to endosomes (Derivery et al, 2009;Gomez and Billadeau, 2009;Harbour et al, 2012;Jia et al, 2012;Monfregola et al, 2010;Monteiro et al, 2013;Ryder et al, 2013), and WASHgenerated F-actin not only regulates the architecture of the endolysosomal system, but also spares specific cargo from lysosomal degradation or missorting (Bartuzi et al, 2016;Derivery et al, 2009Derivery et al, , 2012Duleh and Welch, 2010;Gomez and Billadeau, 2009;Gomez et al, 2012;Monteiro et al, 2013;Zech et al, 2011). WASH is recruited to retromer-positive endosomal subdomains via the interaction of the extended C-terminal tail of FAM21 with the retromer subunit VPS35 (Harbour et al, 2012;Jia et al, 2012).…”

Section: Jmymentioning

confidence: 99%

“…WASH-depleted cells contain cargo-laden tubules (Derivery et al, 2009;Gomez and Billadeau, 2009) and display a collapse of the endolysosomal system . These observations have promoted the hypothesis that WASH-generated F-actin regulates tubule fission through the generation of F-actinmediated forces (Derivery et al, 2009).…”

Section: Jmymentioning

confidence: 99%

“…This is accomplished by two WCA domains interacting with two unique sites on the Arp2/3 complex simultaneously to promote actin nucleation (Padrick et al, 2011). binding WASH homology domain 2 (WHD2), a proline-rich region and C-terminal WCA domain. WASH is intrinsically inactive and exists in a macromolecular pentameric complex named the WASH regulatory complex (SHRC) that also includes FAM21A or FAM21C (WASHC2A and WASHC2C), strumpellin (WASHC5), KIAA1033 (WASHC4) and CCDC53 (WASHC3) (Derivery et al, 2009;Gomez and Billadeau, 2009;Jia et al, 2010) (see poster). Interestingly, the SHRC appears structurally related to the WAVE regulatory complex (WRC), both in terms of complex assembly and the similarity in shape and size as determined by electron microscopy of the two complexes (Jia et al, 2010).…”

Section: Jmymentioning

confidence: 99%

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Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

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165

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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Section: Jmymentioning

confidence: 99%

Section: Jmymentioning

confidence: 99%

Section: Jmymentioning

confidence: 99%

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Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

Self Cite

165

172

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“…8 Cargo specificity is achieved with the assistance of specific regulators and effectors. The TCR recycling pathway has only started to be delineated with the identification of specific mediators, which include Rab35 and its GAP EPI64C 9 and the actin adaptor WASH 10 . Specific combinations of Rabs and SNAREs have been recently associated with recycling endosomes carrying either Lck, or TCRζ and LAT.…”

mentioning

confidence: 99%

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

et al. 2015

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Accumulating evidence underscores the T-cell immune synapse (IS) as a site of intense vesicular trafficking, on which productive signaling and cell activation crucially depend. Although the T-cell antigen receptor (TCR) is known to exploit recycling to accumulate to the IS, the specific pathway that controls this process remains to be elucidated. Here we demonstrate that the small GTPase Rab29 is centrally implicated in TCR trafficking and IS assembly. Rab29 colocalized and interacted with Rab8, Rab11 and IFT20, a component of the intraflagellar transport system that regulates ciliogenesis and participates in TCR recycling in the non-ciliated T cell, as assessed by co-immunoprecipitation and immunofluorescence analysis. Rab29 depletion resulted in the inability of TCRs to undergo recycling to the IS, thereby compromizing IS assembly. Under these conditions, recycling TCRs accumulated in Rab11 + endosomes that failed to polarize to the IS due to defective Rab29-dependent recruitment of the dynein microtubule motor. Remarkably, Rab29 participates in a similar pathway in ciliated cells to promote primary cilium growth and ciliary localization of Smoothened. These results provide a function for Rab29 as a regulator of receptor recycling and identify this GTPase as a shared participant in IS and primary cilium assembly. T-cell activation is triggered by T-cell antigen receptor (TCR) engagement by MHC-bound peptide dispayed by an antigen presenting cell (APC). While a substantial proportion of the TCR has long been known to be associated with recycling endosomes, 1 it is only recently that the central function of this pool has emerged with the finding that, on assembly of the specialized interface with the APC, known as the immune synapse (IS), intracellular TCRs are delivered to this location by polarized recycling. 2 This process ensures a steady supply of TCRs at the IS to sustain signaling for T-cell activation 3 and has been co-opted by other receptors, such as the transferrin receptor (TfR) and the chemokine receptor CXCR4, 4,5 as well as membrane-bound signaling mediators, such as the kinase Lck and the adaptor LAT. 6,7 Receptor recycling is orchestrated by the small GTPases Rab4 and Rab11. 8 Cargo specificity is achieved with the assistance of specific regulators and effectors. The TCR recycling pathway has only started to be delineated with the identification of specific mediators, which include Rab35 and its GAP EPI64C 9 and the actin adaptor WASH 10 . Specific combinations of Rabs and SNAREs have been recently associated with recycling endosomes carrying either Lck, or TCRζ and LAT. 11 We have moreover identified IFT20 12 and other components of the intraflagellar transport (IFT) system, which regulates ciliary assembly and function, 13 as unexpected regulators of TCR recycling in the non-ciliated T cell. 14 Recently a Rab GTPase subfamily, which includes Rab29, Rab32 and Rab38, has been implicated in trafficking of the Salmonella-containing vacuole (SCV) in infected epithelial cells. 15,16 Rab32 and Rab38 ...

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“…This COM MD-CCDC22-CCDC93 (CCC) complex localizes to endosomes through interactions between CCDC22 and CCDC93 with FAM21 (Harbour et al, 2012;Freeman et al, 2014;Phillips-Krawczak et al, 2015), a component of the Wiskott-Aldrich syndrome protein and scar homolog (WASH) complex (Derivery et al, 2009;Gomez and Billadeau, 2009). WASH is a member of the Wiskott-Aldrich syndrome protein Notch family members are transmembrane receptors that mediate essential developmental programs.…”

Section: Introductionmentioning

confidence: 99%