[13] Expression and properties of Rab4 and its effector rabaptin-4 in endocytic recycling

Sluijs, Peter van der; Mohrmann, Karin; Deneka, Magda; Jongeneelen, Mandy

doi:10.1016/s0076-6879(01)29072-7

Cited by 11 publications

(9 citation statements)

References 9 publications

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“…This seems to be consistent with the finding that surface-localised MT1-MMP can be internalised by both clathrin-dependent and -independent pathways (Remacle et al, 2003). Moreover, Rab4 and Rab11, which both regulate recycling of clathrin-dependent cargo (Schlierf et al, 2000;van der Sluijs et al, 2001), did not colocalise with MT1-MMP in the screen. This suggests that uptake of MT1-MMP from the cell surface proceeds mostly via clathrin-independent pathways in primary macrophages.…”

Section: Discussionsupporting

confidence: 89%

A specific subset of RabGTPases controls cell surface exposure of MT1-MMP, extracellular matrix degradation and 3D invasion of macrophages

Wiesner

Azzouzi

Linder

2013

Journal of Cell Science

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SummaryThe matrix metalloproteinase MT1-MMP has a major impact on invasive cell migration in both physiological and pathological settings such as immune cell extravasation or metastasis of cancer cells. Surface-associated MT1-MMP is able to cleave components of the extracellular matrix, which is a prerequisite for proteolytic invasive migration. However, current knowledge on the molecular mechanisms that regulate MT1-MMP trafficking to and from the cell surface is limited. We have identified three members of the RabGTPase family, Rab5a, Rab8a and Rab14, as crucial regulators of MT1-MMP trafficking and function in primary human macrophages. Both overexpressed and endogenous forms show prominent colocalisation with MT1-MMP-positive vesicles, whereas expression of mutant constructs, as well as siRNA-induced knockdown, reveal that these RabGTPases are crucial in the regulation of MT1-MMP surface exposure, contact of MT1-MMP-positive vesicles with podosomes, extracellular matrix degradation in two and three dimensions, as well as three-dimensional proteolytic invasion of macrophages. Collectively, our results identify Rab5a, Rab8a and Rab14 as major regulators of MT1-MMP trafficking and invasive migration of primary human macrophages, which could be promising potential targets for manipulation of immune cell invasion.

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Section: Discussionsupporting

confidence: 89%

A specific subset of RabGTPases controls cell surface exposure of MT1-MMP, extracellular matrix degradation and 3D invasion of macrophages

Wiesner

Azzouzi

Linder

2013

Journal of Cell Science

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“…For example, rab5a is present on endosomes, is involved in endosome-endosome fusion (Gournier et al, 1998), in linking early endosomes to microtubules, and in minus-end-directed movement (Nielsen et al, 1999), although rab5a has not yet been demonstrated to interact with any motor protein. Rab 4 and rab 11 are endosome-associated proteins thought to be involved in recycling (Van Der Sluijs et al, 1991;McCaffrey et al, 2001;Peden et al, 2004) but their precise roles and which of the many possible effectors are relevant for this function remains unclear (Nagelkerken et al, 2000;Cormont et al, 2001;van der Sluijs et al, 2001;Fouraux et al, 2004;Peden et al, 2004). The present data suggest that hrs may link endosomes to actin through actinin-4, BERP, and myosin Vb.…”

Section: Discussionmentioning

confidence: 61%

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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“…Extending these morphological observations to endosomal function in DS fibroblasts, our results provide several lines of evidence of early endocytic pathway activation in the DS cells. These include: 1) increased expression of rab5 and rab4, which regulate endocytic uptake and homotypic fusion and fast endosomal recycling, respectively 42,46,48,57,62 ; 2) early endosomal enlargement suggestive of enhanced early endosomal fusion; 3) an increase in receptor-mediated and fluid phase endocytic uptake; and 4) an increase in the presence of MPR46 (and lysosomal hydrolases) to early endosomes. In DS fibroblasts, we observed abnormally large rab5-positive endosomes by immunocytochemistry and, by Western blot analyses, increased rab5-immunoreac- Figure 8.…”

Section: Discussionmentioning

confidence: 99%

Down Syndrome Fibroblast Model of Alzheimer-Related Endosome Pathology

Cataldo

Mathews

Boiteau

et al. 2008

The American Journal of Pathology

162

150

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Endocytic dysfunction is an early pathological change in Alzheimer's disease (AD) and Down's syndrome (DS). Using primary fibroblasts from DS individuals , we explored the interactions among endocytic compartments that are altered in AD and assessed their functional consequences in AD pathogenesis. We found that , like neurons in both AD and DS brains , DS fibroblasts exhibit increased endocytic uptake , fusion , and recycling , and trafficking of lysosomal hydrolases to rab5-positive early endosomes. Moreover , late endosomes identified using antibodies to rab7 and lysobisphosphatidic acid increased in number and appeared as enlarged , perinuclear vacuoles , resembling those in neurons of both AD and DS brains. In control fibroblasts , similar enlargement of rab5-, rab7-, and lysobisphosphatidic acid-positive endosomes was induced when endocytosis and endosomal fusion were increased by expression of either a rab5 or an active rab5 mutant , suggesting that persistent endocytic activation results in late endocytic dysfunction. Conversely , expression of a rab5 mutant that inhibits endocytic uptake reversed early and late endosomal abnormalities in DS fibroblasts. Our results indicate that DS fibroblasts recapitulate the neuronal endocytic dysfunction of AD and DS , suggesting that increased trafficking from early endosomes can account , in part , for downstream endocytic perturbations that occur in neurons in both AD and DS brains.

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[13] Expression and properties of Rab4 and its effector rabaptin-4 in endocytic recycling

Cited by 11 publications

References 9 publications

A specific subset of RabGTPases controls cell surface exposure of MT1-MMP, extracellular matrix degradation and 3D invasion of macrophages

A specific subset of RabGTPases controls cell surface exposure of MT1-MMP, extracellular matrix degradation and 3D invasion of macrophages

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

Down Syndrome Fibroblast Model of Alzheimer-Related Endosome Pathology

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