The Rilp-like proteins Rilpl1 and Rilpl2 regulate ciliary membrane content

Schaub, Johanna; Stearns, Tim

doi:10.1091/mbc.e12-08-0598

Cited by 57 publications

(66 citation statements)

References 50 publications

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“…Structural Basis for Inability of MyoVb to Bind RILPL2-The RILPL2 (Rab interacting lysosomal protein-like 2) is a centrosomal and ciliary protein that regulates the protein content of the primary cilium (58). RILPL2 differs from RILP by lacking the Rab7-interacting region and therefore is not involved with lysosomal morphology (59).…”

mentioning

confidence: 99%

Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors

Nascimento

Trindade

Tonoli

et al. 2013

Journal of Biological Chemistry

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Background: MyoVs are molecular motors widely distributed in eukaryotic cells responsible for membrane trafficking and intracellular transport. Results: The cargo-binding domain from human MyoV paralogs was structurally and biophysically characterized. Conclusion: We identified singular structural changes and molecular events conferring functional differentiation and modulating cargo binding. Significance: This work provides structural insights into cargo recognition and regulatory mechanisms in MyoVs.

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mentioning

confidence: 99%

Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors

Nascimento

Trindade

Tonoli

et al. 2013

Journal of Biological Chemistry

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“…Supportively, when RAB10 was depleted from ciliated mouse cells lacking RAB8A and RAB8B, ciliation frequency was greatly reduced, indicating that RAB10 may compensate for the loss of RAB8A/B in ciliogenesis in vivo . This view is supported by a recent study showing that RAB8 and RAB10 are both phosphorylated by the Parkinson's disease kinase LRRK2 and interact with RILP1 and RILP2, two regulators of ciliary membrane protein content . In fibroblasts from knock‐in mice expressing a disease‐causing, hyperactive variant of LRRK2, a two‐fold reduction in ciliation frequency was observed, implicating LRRK2 and its substrates in ciliogenesis .…”

Section: Assembly Of Primary Ciliamentioning

confidence: 84%

Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins

2018

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Primary cilia are antenna-like sensory organelles that regulate a substantial number of cellular signalling pathways in vertebrates, both during embryonic development as well as in adulthood, and mutations in genes coding for ciliary proteins are causative of an expanding group of pleiotropic diseases known as ciliopathies. Cilia consist of a microtubule-based axoneme core, which is subtended by a basal body and covered by a bilayer lipid membrane of unique protein and lipid composition. Cilia are dynamic organelles, and the ability of cells to regulate ciliary protein and lipid content in response to specific cellular and environmental cues is crucial for balancing ciliary signalling output. Here we discuss mechanisms involved in regulation of ciliary membrane protein trafficking and signalling, with main focus on kinesin-2 and kinesin-3 family members.

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“…RILPL1 and RILPL2 are two RILP-related proteins that bind much more tightly to phosphorylated Rab8 and Rab10 proteins than to their non-phosphorylated states (Steger et al, 2017), but little is known about their cellular roles. Both RILPL1 and RILPL2 were reported to be ciliary proteins involved in regulating ciliary content (Schaub & Stearns, 2013).…”

Section: Phosphorylation Of Rab Proteins Blocks Their Abilities To Inmentioning

confidence: 99%

LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade

Izumi

Dhekne

Vides

et al. 2020

Preprint

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Activating mutations in LRRK2 kinase cause Parkinson's disease. Pathogenic LRRK2 phosphorylates a subset of Rab GTPases and blocks ciliogenesis. Thus, defining novel phospho-Rab interacting partners is critical to our understanding of the molecular basis of LRRK2 pathogenesis. RILPL2 binds with strong preference to LRRK2-phosphorylated Rab8A and Rab10. RILPL2 is a binding partner of the motor protein and Rab effector, Myosin Va. We show here that the globular tail domain of Myosin Va also contains a high affinity binding site for LRRK2-phosphorylated Rab10, and certain tissue-specific Myosin Va isoforms strongly prefer to bind phosphorylated Rab10. In the presence of pathogenic LRRK2, RILPL2 relocalizes to the peri-centriolar region in a phosphoRab10-and Myosin Vadependent manner. In the absence of phosphoRab10, expression of RILPL2 or depletion of Myosin Va increase centriolar RILPL2 levels, and either condition is sufficient to block ciliogenesis in RPE cells. These experiments show that LRRK2 generated phosphoRab10 dramatically redistributes Myosin Va-RILPL2 complexes to the mother centriole, which may sequester Myosin Va and RILPL2 in a manner that blocks their normal roles in ciliogenesis.

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The Rilp-like proteins Rilpl1 and Rilpl2 regulate ciliary membrane content

Cited by 57 publications

References 50 publications

Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors

Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors

Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins

LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade

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