The Rab Interacting Lysosomal Protein (RILP) Homology Domain Functions as a Novel Effector Domain for Small GTPase Rab36

Matsui, Takahide; Ohbayashi, Norihiko; Fukuda, Mitsunori

doi:10.1074/jbc.m112.370544

Cited by 73 publications

(82 citation statements)

References 44 publications

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“…Consistent with 56, we were unable to detect Rab36 expression in HeLa and so we focused on Rab7 and Rab34. Under normal growth conditions, expression of GFP‐Rab34 promoted the robust peri‐nuclear accumulation of lysosomes compared to expression of GFP alone, whereas expression of GFP‐Rab7 had no significant effect (Fig 3A).…”

Section: Resultssupporting

confidence: 56%

Folliculin directs the formation of a Rab34–RILP complex to control the nutrient‐dependent dynamic distribution of lysosomes

et al. 2016

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The spatial distribution of lysosomes is important for their function and is, in part, controlled by cellular nutrient status. Here, we show that the lysosome associated Birt–Hoge–Dubé (BHD) syndrome renal tumour suppressor folliculin (FLCN) regulates this process. FLCN promotes the peri‐nuclear clustering of lysosomes following serum and amino acid withdrawal and is supported by the predominantly Golgi‐associated small GTPase Rab34. Rab34‐positive peri‐nuclear membranes contact lysosomes and cause a reduction in lysosome motility and knockdown of FLCN inhibits Rab34‐induced peri‐nuclear lysosome clustering. FLCN interacts directly via its C‐terminal DENN domain with the Rab34 effector RILP. Using purified recombinant proteins, we show that the FLCN‐DENN domain does not act as a GEF for Rab34, but rather, loads active Rab34 onto RILP. We propose a model whereby starvation‐induced FLCN association with lysosomes drives the formation of contact sites between lysosomes and Rab34‐positive peri‐nuclear membranes that restrict lysosome motility and thus promote their retention in this region of the cell.

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Section: Resultssupporting

confidence: 56%

Folliculin directs the formation of a Rab34–RILP complex to control the nutrient‐dependent dynamic distribution of lysosomes

et al. 2016

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“…This surface in SD-1 is thus an isoform-specific interaction site. Interestingly, it has been shown that this region of Myo5A is involved in binding to the isoform-specific adaptor RILPL2 (15) that binds to Rab36 (16).…”

Section: Resultsmentioning

confidence: 99%

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Pylypenko

Attanda

Gauquelin

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

108

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Specific recognition of the cargo that molecular motors transport or tether to cytoskeleton tracks allows them to perform precise cellular functions at particular times and positions in cells. However, very little is known about how evolution has favored conservation of functions for some isoforms, while also allowing for the generation of new recognition sites and specialized cellular functions. Here we present several crystal structures of the myosin Va or the myosin Vb globular tail domain (GTD) that gives insights into how the motor is linked to the recycling membrane compartments via Rab11 or to the melanosome membrane via recognition of the melanophilin adaptor that binds to Rab27a. The structures illustrate how the Rab11-binding site has been conserved during evolution and how divergence at another site of the GTD allows more specific interactions such as the specific recognition of melanophilin by the myosin Va isoform. With atomic structural insights, these structures also show how either the partner or the GTD structural plasticity upon association is critical for selective recruitment of the motor.GTPases | DIL motif | Rab effector | intracellular traffic D irected movement is essential for life, and cytoskeletonbased motors generate mechanical force and motion to precisely organize the cell. Their coordinated actions allow them to play key roles in nearly every physiological process. Class V myosins (Myo5) and the related plant class XI myosins are a group of multifunctional actin-based nanomotors that have evolved from one of the three ancient myosin subfamilies (1). The motor domain and extended lever arm of these myosins is followed by a coiled coil dimerizing region and the C-terminal globular tail domain (GTD) that primarily plays a role in selective cargo recruitment. Little is known, however, about how this GTD sequence has evolved to serve both a role in regulation of the motor activity (2, 3) and specific recruitment of the motor, which is critical to control precisely in space and time when the motor is activated for different cellular functions.

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“…Interestingly, RILP also binds the tethering HOPS complex, thus coupling membrane tethering to microtubule minus-end transport (van der Kant et al 2013). RILP is also an effector of Rab36 that regulates retrograde melanosome transport in melanocytes (Matsui et al 2012), indicating that effectors can be shared between different Rab proteins localized to distinct intracellular compartments. Rab9 interaction with a Golgi-tethering factor, GCC185, promotes interaction with Rab6, Arl1, and the CLASP microtubule-anchoring protein and is suggested to integrate dynein-mediated delivery with docking of endosome-derived vesicles to the Golgi (Hayes et al 2009).…”

Section: Rab Gtpases and Microtubule-dependent Translocationmentioning

confidence: 99%

Rab Proteins and the Compartmentalization of the Endosomal System

Wandinger‐Ness

Zerial

2014

Cold Spring Harbor Perspectives in Biology

503

469

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Of the approximately 70 human Rab GTPases, nearly three-quarters are involved in endocytic trafficking. Significant plasticity in endosomal membrane transport pathways is closely coupled to receptor signaling and Rab GTPase-regulated scaffolds. Here we review current literature pertaining to endocytic Rab GTPase localizations, functions, and coordination with regulatory proteins and effectors. The roles of Rab GTPases in (1) compartmentalization of the endocytic pathway into early, recycling, late, and lysosomal routes; (2) coordination of individual transport steps from vesicle budding to fusion; (3) effector interactomes; and (4) integration of GTPase and signaling cascades are discussed.

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The Rab Interacting Lysosomal Protein (RILP) Homology Domain Functions as a Novel Effector Domain for Small GTPase Rab36

Cited by 73 publications

References 44 publications

Folliculin directs the formation of a Rab34–RILP complex to control the nutrient‐dependent dynamic distribution of lysosomes

Folliculin directs the formation of a Rab34–RILP complex to control the nutrient‐dependent dynamic distribution of lysosomes

Structural basis of myosin V Rab GTPase-dependent cargo recognition

Rab Proteins and the Compartmentalization of the Endosomal System

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