Rabenosyn-5 and EHD1 Interact and Sequentially Regulate Protein Recycling to the Plasma Membrane

Naslavsky, Naava; Boehm, Markus; Backlund, Peter S.; Caplan, Steve

doi:10.1091/mbc.e03-10-0733

Cited by 130 publications

(215 citation statements)

References 54 publications

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“…In addition, EHD1/mRme-1 interacts through its EH domain with an actin-associated protein EHBP1 that, like EHD1/mRme-1 itself, is required for insulinstimulated translocation of the GLUT4 to the plasma membrane (13). Finally, EHD1/mRme-1 has been shown to interact through its EH domain with Rabenosyn-5, a Rab4/Rab5 effector that plays an important role in transport from early endosomes to recycling endosomes (23).…”

Section: Discussionmentioning

confidence: 99%

ATP Binding Regulates Oligomerization and Endosome Association of RME-1 Family Proteins

Lee

Zhao

Scarselletta

et al. 2005

Journal of Biological Chemistry

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Members of the RME-1/mRme-1/EHD1 protein family have recently been shown to function in the recycling of membrane proteins from recycling endosomes to the plasma membrane. RME-1 family proteins are normally found in close association with recycling endosomes and the vesicles and tubules emanating from these endosomes, consistent with the proposal that these proteins directly participate in endosomal transport. RME-1 family proteins contain a C-terminal EH (eps15 homology) domain thought to be involved in linking RME-1 to other endocytic proteins, a coiled-coil domain thought to be involved in homo-oligomerization and an N-terminal Ploop domain thought to mediate nucleotide binding. In the present study, we show that both Caenorhabditis elegans and mouse RME-1 proteins bind and hydrolyze ATP. No significant GTP binding or hydrolysis was detected. Mutation or deletion of the ATP-binding P-loop prevented RME-1 oligomerization and at the same time dissociated RME-1 from endosomes. In addition, ATP depletion caused RME-1 to lose its endosome association in the cell, resulting in cytosolic localization. Taken together, these results indicate that ATP binding is required for oligomerization of mRme-1/EHD1, which in turn is required for its association with endosomes.

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Section: Discussionmentioning

confidence: 99%

ATP Binding Regulates Oligomerization and Endosome Association of RME-1 Family Proteins

Lee

Zhao

Scarselletta

et al. 2005

Journal of Biological Chemistry

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“…Gene Knockdown by Silencing RNA (siRNA)-Custom design oligonucleotide duplexes targeting human EHD1 (Naslavsky et al (15)) and ON-TARGETplus SMARTpool siRNA targeting MICAL-L1 and Crmp2 (Dharmacon) were transfected for 72 h using Dharmafect (Dharmacon) as described previously (16).…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies have determined that the EH domains of the C-terminal EHD proteins have a highly positively charged surface (12) and selectively interact with NPF motifs followed by clusters of acidic residues (13,14). Moreover, EHD proteins coordinate endocytic transport with Rab proteins through their interactions with common effectors that contain such NPF motifs (9,15). More recently, it was demonstrated that EHD1 interacts with the NPF-containing MICAL family protein, MICAL-L1, a Rab8 effector that localizes to EHD1-containing tubules and regulates endocytic transport and recycling (16).…”

mentioning

confidence: 99%

Collapsin Response Mediator Protein-2 (Crmp2) Regulates Trafficking by Linking Endocytic Regulatory Proteins to Dynein Motors

Rahajeng

Giridharan

Naslavsky

et al. 2010

Journal of Biological Chemistry

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Endocytosis is a conserved cellular process in which nutrients, lipids, and receptors are internalized and transported to early endosomes, where they are sorted and either channeled to degradative pathways or recycled to the plasma membrane. MICAL-L1 and EHD1 are important regulatory proteins that control key endocytic transport steps. However, the precise mechanisms by which they mediate transport, and particularly the mode by which they connect to motor proteins, have remained enigmatic. Here we have identified the collapsin response mediator protein-2 (Crmp2) as an interaction partner of MICAL-L1 in non-neuronal cells. Crmp2 interacts with tubulin dimers and kinesin and negatively regulates dynein-based transport in neuronal cells, but its expression and function in non-neuronal cells have remained poorly characterized. Upon Crmp2 depletion, we observed dramatic relocalization of internalized transferrin (Tf) from peripheral vesicles to the endocytic recycling compartment (ERC), similar to the effect of depleting either MICAL-L1 or EHD1. Moreover, Tf relocalization to the ERC could be inhibited by interfering with microtubule polymerization, consistent with a role for uncoupled motor proteinbased transport upon depletion of Crmp2, MICAL-L1, or EHD1. Finally, transfection of dynamitin, a component of the dynactin complex whose overexpression inhibits dynein activity, prevented the relocalization of internalized Tf to the ERC upon depletion of Crmp2, MICAL-L1, or EHD1. These data provide the first trafficking regulatory role for Crmp2 in non-neuronal cells and support a model in which Crmp2 is an important endocytic regulatory protein that links MICAL-L1⅐EHD1-based vesicular transport to dynein motors.The complexity of the endocytic pathways has broadened in recent years upon discovery of the involvement of the four C-terminal Eps 15 homology domain (EHD) 3 proteins (reviewed in Ref. 1). Since the single Caenorhabditis elegans ortholog (known as RME-1) was originally identified as a regulator of yolk receptor recycling (2), its closest mammalian homolog, EHD1, was found to regulate the recycling of receptors that traverse both the clathrin-dependent (3, 4) and the clathrin-independent (5, 6) internalization pathways. Despite similarities to the Ras family of GTP-binding proteins (5, 7), EHD proteins bind and hydrolyze ATP (7-9), a function necessary for their localization to tubular and vesicular membranes (5,7,10).Proteins that contain EH domains interact with the tripeptide asparagine-proline-phenylalanine (NPF) (11). Recent studies have determined that the EH domains of the C-terminal EHD proteins have a highly positively charged surface (12) and selectively interact with NPF motifs followed by clusters of acidic residues (13, 14). Moreover, EHD proteins coordinate endocytic transport with Rab proteins through their interactions with common effectors that contain such NPF motifs (9, 15). More recently, it was demonstrated that EHD1 interacts with the NPF-containing MICAL family protein, MICAL-L1, a Rab8 ef...

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“…Rab GTPases and Rab effectors are tightly linked in all components of the endosomal trafficking system, and have long been known to coordinate vesicular trafficking (65,66). Furthermore, both Rab and Rab effectors are known binding partners of EHD proteins (46,(67)(68)(69). Currently, there are Ͼ60 Rab GTPases with an equal number of Rab effectors.…”

Section: Discussionmentioning

confidence: 99%

“…EHD3 Co-immunoprecipitates with Cav3.1 and Cav3.2-In non-cardiac tissue, EHD proteins are linked with a host of membrane ion channels, transporters, and receptors (4,(45)(46)(47)(48). However, loss of Ca V 3.1 and Ca V 3.2 expression and targeting in EHD3 cKO atria may represent an indirect response to myocyte remodeling in the face of altered cell trafficking pathways.…”

Section: Ehd3 Is Required For Ca V 31 and Ca V 32 Targeting In Atrialmentioning

confidence: 99%

Eps15 Homology Domain-containing Protein 3 Regulates Cardiac T-type Ca2+ Channel Targeting and Function in the Atria

Curran

Musa

Kline

et al. 2015

Journal of Biological Chemistry

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Rabenosyn-5 and EHD1 Interact and Sequentially Regulate Protein Recycling to the Plasma Membrane

Cited by 130 publications

References 54 publications

ATP Binding Regulates Oligomerization and Endosome Association of RME-1 Family Proteins

ATP Binding Regulates Oligomerization and Endosome Association of RME-1 Family Proteins

Collapsin Response Mediator Protein-2 (Crmp2) Regulates Trafficking by Linking Endocytic Regulatory Proteins to Dynein Motors

Eps15 Homology Domain-containing Protein 3 Regulates Cardiac T-type Ca2+ Channel Targeting and Function in the Atria

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