Actin-Dependent Propulsion of Endosomes and Lysosomes by Recruitment of N-Wasp✪

Taunton, Jack; Rowning, Brian A.; Coughlin, Margaret; Wu, Michael; Moon, Randall T.; Mitchison, Timothy J.; Larabell, Carolyn A.

doi:10.1083/jcb.148.3.519

Cited by 403 publications

(352 citation statements)

References 35 publications

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“…CaM may regulate the actin cytoskeleton through its effectors, thereby controlling endo-and exocytic pathways (Guerin and de Chastellier, 2000;Taunton et al, 2000;Qualmann and Kessels, 2002;Merrifield et al, 2004;Chang et al, 2005). The assembly of actin coats on different populations of endosomes and vacuoles has been reported as a result of a variety of stimuli in distinct cell types throughout the endocytic compartment.…”

Section: Cam and Actin Dynamics In The Early Endosomesmentioning

confidence: 99%

“…These proteins provide a link between Cdc42 and Rac1 activation, respectively, and regulation of actin polymerization (Machesky and Insall, 1999;Miki et al, 2000;Higgs and Pollard, 2001). Indeed, the N-WASP/SCAR/ WAVE family of proteins have been implicated in promoting motility of endosomes and other organelles (Taunton et al, 2000;Southwick et al, 2003). Moreover, cortactin also has NPF activity, binds F-actin and has been implicated in the motility of endosomes (Daly, 2004, and references therein).…”

Section: Molecular Machinery Involved In the Formation Of The Actin Cmentioning

confidence: 99%

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Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

Lladó

Timpson

Muga

et al. 2008

MBoC

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The intracellular trafficking of the epidermal growth factor receptor (EGFR) is regulated by a cross-talk between calmodulin (CaM) and protein kinase C␦ (PKC␦). On inhibition of CaM, PKC␦ promotes the formation of enlarged early endosomes and blocks EGFR recycling and degradation. Here, we show that PKC␦ impairs EGFR trafficking due to the formation of an F-actin coat surrounding early endosomes. The PKC␦-induced polymerization of actin is orchestrated by the Arp2/3 complex and requires the interaction of cortactin with PKC␦. Accordingly, inhibition of actin polymerization by using cytochalasin D or by overexpression of active cofilin, restored the normal morphology of the organelle and the recycling of EGFR. Similar results were obtained after down-regulation of cortactin and the sequestration of the Arp2/3 complex. Furthermore we demonstrate an interaction of cortactin with CaM and PKC␦, the latter being dependent on CaM inhibition. In summary, this study provides the first evidence that CaM and PKC␦ organize actin dynamics in the early endosomal compartment, thereby regulating the intracellular trafficking of EGFR. INTRODUCTIONCalmodulin (CaM) is a ubiquitous small calcium sensor that regulates a variety of cellular processes in a spatial and temporal manner within the cell (Toutenhoofd and Strehler, 2000). Microenvironment variations in the concentration of CaM may be critical to the control of cellular processes that involve specific and high-affinity CaM-binding proteins (Berridge et al., 2000;Carafoli, 2002;Kahl and Means, 2003).We have previously shown that CaM is crucial to the regulation of the dynamics of endosomes. In particular, in the presence of W13, a highly specific CaM antagonist, trafficking is blocked in early endosomes, thereby interfering with transport toward degradation and recycling pathways. This blockage was associated with a dramatic alteration of the morphology and size of early endosomes (Tebar et al., 2002;Lladó et al., 2004). Furthermore we showed that a cross-talk between CaM and protein kinase C␦ (PKC␦) is involved in the regulation of the budding from the early endocytic compartment (Lladó et al., 2004).Several lines of evidence implicate the actin cytoskeleton in the CaM-and PKC␦-mediated regulation of vesicular trafficking. Because actin contributes to the maintenance of organelle stability (Apodaca, 2001), swelling and morphological changes observed in response to CaM/PKC␦ activity (Lladó et al., 2004) may involve altered actin dynamics. Moreover, several CaM-binding proteins and PKC␦ substrates are also actin-binding proteins, including ␣-actinin, adducin, and myristoylated alanine-rich protein kinase C substrate (MARCKS) (Chakravarthy et al., 1999). Finally, RhoGTPases and CaM-binding proteins responsible for fusion-fission events during vesicular trafficking also depend on actin filaments for pinch-off and vesicular movement (Mayorga et al., 1994;Mu et al., 1995;Colombo et al., 1997;Ridley, 2001;Burgoyne and Clague, 2003;Lawe et al., 2003;Donaldson, 2005).The actin cytosk...

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Section: Cam and Actin Dynamics In The Early Endosomesmentioning

confidence: 99%

Section: Molecular Machinery Involved In the Formation Of The Actin Cmentioning

confidence: 99%

Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

Lladó

Timpson

Muga

et al. 2008

MBoC

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“…However, some yeast mutants that disrupt actin organization have no effect on endocytosis (Riezman et al, 1997), and some suppressors of an endocytosis mutant that also affects actin organization (end5) can rescue one or the other phenotype, but not both, suggesting that they are separable (Riezman et al, 1997). In mammalian cells, many reports exist describing the necessity, or lack thereof, of the intact actin cytoskeleton for endocytosis (Durrbach et al, 1996;Lamaze et al, 1997;Fujimoto et al, 2000;Qualmann et al, 2000;Taunton et al, 2000;Lanzetti et al, 2001;Zaslaver et al, 2001). These reports have concentrated on the effect of disruption of the integrity of the actin cytoskeleton on early events in the endocytic process such as vesicle budding from the plasma membrane, but they have not focused on later events such as the motility of endosomes.…”

Section: Introductionmentioning

confidence: 99%

CART: An Hrs/Actinin-4/BERP/Myosin V Protein Complex Required for Efficient Receptor Recycling

Yan

Wei

Kujala

et al. 2005

MBoC

115

121

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Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors. INTRODUCTIONEndocytosis is required for the uptake of essential nutrients from the extracellular environment as well as for retrieval of proteins and lipids that are added to the plasma membrane during fusion of regulated and constitutive secretory vesicles (De Camilli and Takei, 1996;Koenig and Ikeda, 1996;Robinson et al., 1996;Mukherjee et al., 1997;Schmid, 1997;Betz and Angleson, 1998;Koenig et al., 1998;Stoorvogel, 1998;D'Hondt et al., 2000;Gruenberg, 2001). The endocytic pathway can be separated into numerous stages based on the movement of cargo and the identification of morphologically defined compartments (De Camilli and Takei, 1996;Koenig and Ikeda, 1996;Robinson et al., 1996;Mukherjee et al., 1997;Schmid, 1997;Betz and Angleson, 1998;Koenig et al., 1998;Stoorvogel, 1998;D'Hondt et al., 2000;Gruenberg, 2001). Early events in the endocytic process include membrane invagination and vesicle budding from the plasma membrane, formation of transport vesicles, and fusion with early endosomes. Later events include cargo sorting, and additional transport/fusion steps, including those responsible for transport to the lysosome for degradation, and those responsible for recycling back to various compartments (De Camilli and Takei, 1996;Koenig and Ikeda, 1996;Robinson et al., 1996;Mukherjee et al., 1997;Schmid, 1997;Betz and Angleson, 1998;Koenig et al., 1998;Stoorvogel, 1998;D'Hondt et al., 2000;Gruenberg, 2001). Although much progress has been made in elucidating the molecular processes involved in early endocytic events, such as those involved in the genesis of clathrin-coated endocytic transport vesicles, an equally clear understanding of later events remains elusive.The early endosome is a crucial point in the endocytic pathway to sort cargo for transport to late endosomes for eventual degradation in the...

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“…These actin comets are not specific to bacteria. Endocytic vesicles also recruit N-WASP and form actin comets to move inside cells [Taunton et al, 2000]. Recently, proteins involved in endocytic vesicle transport, such as cortactin, Pan1p (yeast homolog of Eps15), and Abp1p, were found to associate with Arp2/3 complex [Duncan et al, 2001;Goode et al, 2001;Uruno et al, 2001;Weaver et al, 2001].…”

Section: Simplified Model Of Actin Cytoskeleton Reorganization: Actinmentioning

confidence: 99%

Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2/3 complex and WASP/WAVE proteins

Suetsugu

Miki

Takenawa

2002

Cell Motil. Cytoskeleton

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Actin-Dependent Propulsion of Endosomes and Lysosomes by Recruitment of N-Wasp✪

Cited by 403 publications

References 35 publications

Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

Protein Kinase Cδ and Calmodulin Regulate Epidermal Growth Factor Receptor Recycling from Early Endosomes through Arp2/3 Complex and Cortactin

CART: An Hrs/Actinin-4/BERP/Myosin V Protein Complex Required for Efficient Receptor Recycling

Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2/3 complex and WASP/WAVE proteins

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