Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22

Woller, Barbara; Luiskandl, Susan; Popović, Milica; Prieler, Barbara Eva Maria; Ikonge, Gloria; Mutzl, Michaela; Rehmann, Holger; Herbst, Ruth

doi:10.1016/j.bbamcr.2011.03.005

Cited by 18 publications

(33 citation statements)

References 49 publications

(62 reference statements)

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“…We found that RINL/WT interacted with dominant-negative Rab5b/S34N using the yeast two-hybrid system as reported previously [14], while either RINL/DP_AA or YT_AA reduced this interaction (data not shown). Furthermore, the increase in GTP-Rab5b after co-expression of RINL was completely abolished by mutations of the VPS9 domain (Fig.…”

Section: Resultssupporting

confidence: 87%

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RINL, Guanine Nucleotide Exchange Factor Rab5-Subfamily, Is Involved in the EphA8-Degradation Pathway with Odin

et al. 2012

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The Rab family of small guanosine triphosphatases (GTPases) plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs). Ras and Rab interactor (or Ras interaction/interference)-like (RINL), which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM) domain-containing (Anks) protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin.

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Section: Resultssupporting

confidence: 87%

“…Quite recently, RINL was reported to act as a GEF for both Rab5 and Rab22 GTPases in vitro , stimulating the dissociation rate of GDP from these GTPases [14]. We confirmed the GEF activity of RINL for Rab5 subfamily proteins by measuring the formation of GTP-bound forms of these proteins (Figure S1).…”

Section: Resultssupporting

confidence: 78%

RINL, Guanine Nucleotide Exchange Factor Rab5-Subfamily, Is Involved in the EphA8-Degradation Pathway with Odin

et al. 2012

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“…Rab11 S25N was provided by Dr M. Granato (University of Pennsylvania, Philadelphia, PA, USA). Rab5 was cloned into pEGFP‐C2 (Clontech, Palo Alto, CA, USA) using Eco RI . SBP‐MuSK (wt) was generated by introducing the SBP sequence into a 10 amino acid alternative insert in the extracellular domain of MuSK by PCR.…”

Section: Methodsmentioning

confidence: 99%

Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via clathrin‐dependent pathways, Arf6 and actin

et al. 2013

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Muscle-specific kinase (MuSK), a receptor tyrosine kinase, is the key player during the formation of the neuromuscular junction. Signal transduction events downstream of MuSK activation induce both pre-and postsynaptic differentiation, which, most prominently, includes the clustering of acetylcholine receptors at synaptic sites. More recently, regulated MuSK endocytosis and degradation have been implicated as crucial events for MuSK signalling activity, implicating a cross-talk between signalling and endocytosis. In the present study, we use a live imaging approach to study MuSK endocytosis. We find that MuSK is internalized via a clathrin-, dynamin-dependent pathway. MuSK is transported to Rab7-positive endosomes for degradation and recycled via Rab4-and Rab11-positive vesicles. MuSK activation by Dok7 mildly affects the localization of MuSK on the cell surface but has no effect on the rate of MuSK internalization. Interestingly, MuSK colocalizes with actin and Arf6 at the cell surface and during endosomal trafficking. Disruption of the actin cytoskeleton or the proper function of Arf6 concentrates MuSK in cell protrusions. Moreover, inhibition of Arf6 or cytoskeletal rearrangements impairs acetylcholine receptor clustering and phosphorylation. These results suggest that MuSK uses both classical and nonclassical endosomal pathways that involve a variety of different components of the endosomal machinery.Structured digital abstractMuSK and Arf6 colocalize by fluorescence microscopy (View Interaction: 1, 2)MuSK and Rab4 colocalize by fluorescence microscopy (View interaction)MuSK and Rab11 colocalize by fluorescence microscopy (View interaction)MuSK and Rab7 colocalize by fluorescence microscopy (View interaction)

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“…In the absence of Rabex-5, Rab22 and Rab5 show only partial colocalization, whereas cells overexpressing both Rab22 and Rab5 exhibited enlarged endosomes, suggesting that these two Rab GTPases work cooperatively in the regulation of endosome fusion and the trafficking of epidermal growth factor receptors (28). A recent study demonstrated that RIN (Ras and Rab interactor) family protein Rin-like (Rinl) binds to the nucleotide-free form of Rab5a and Rab22, and Rinl has GEF activity toward both proteins, but it acts with higher efficiency on Rab22 (29). The functional relationship between Rin1 and Rabex-5 is not currently known.…”

Section: Guanine Nucleotide Exchange Factor Cascadesmentioning

confidence: 99%

GTPase Networks in Membrane Traffic

Mizuno-Yamasaki

Rivera‐Molina

Novick

2012

Annu. Rev. Biochem.

316

309

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Members of the Rab or ARF/Sar branches of the Ras GTPase super-family regulate almost every step of intracellular membrane traffic. A rapidly growing body of evidence indicates that these GTPases do not act as lone agents but are networked to one another through a variety of mechanisms to coordinate the individual events of one stage of transport and to link together the different stages of an entire transport pathway. These mechanisms include guanine nucleotide exchange factor (GEF) cascades, GTPase-activating protein (GAP) cascades, effectors that bind to multiple GTPases, and positive-feedback loops generated by exchange factor-effector interactions. Together these mechanisms can lead to an ordered series of transitions from one GTPase to the next. As each GTPase recruits a unique set of effectors, these transitions help to define changes in the functionality of the membrane compartments with which they are associated.

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Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22

Cited by 18 publications

References 49 publications

RINL, Guanine Nucleotide Exchange Factor Rab5-Subfamily, Is Involved in the EphA8-Degradation Pathway with Odin

RINL, Guanine Nucleotide Exchange Factor Rab5-Subfamily, Is Involved in the EphA8-Degradation Pathway with Odin

Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via clathrin‐dependent pathways, Arf6 and actin

GTPase Networks in Membrane Traffic

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