Posttranslational modifications of Rab GTPases help their insertion into membranes

Pylypenko, Olena; Goud, Bruno

doi:10.1073/pnas.1202494109

Cited by 9 publications

(9 citation statements)

References 26 publications

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“…This is in accordance with how the Rab-GTP-Rab-GDP molecular switch is associated with Rab proteins alternating between being attached to membrane and being soluble, cytosolic proteins (Pylypenko and Goud, 2012;Seabra and Wasmeier, 2004).…”

Section: Discussion Localization Of Rab23 At the Primary Ciliumsupporting

confidence: 54%

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

Lim

Tang

2015

Journal of Cell Science

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The small GTPase Rab23 is an antagonist of sonic hedgehog (Shh) signaling during mouse development. Given that modulation of Shh signaling depends on the normal functioning of the primary cilium, and overexpression of Evi5L, a putative Rab23 GTPase-activating protein (GAP), leads to reduced ciliogenesis, Rab23 could have a role at the primary cilium. Here, we found that wild-type Rab23 and the constitutively active Rab23 Q68L mutant were enriched at the primary cilium. Therefore, we tested the role of Rab23 in the ciliary targeting of known cargoes and found that ciliary localization of the kinesin-2 motor protein Kif17 was disrupted in Rab23-depleted cells. Co-immunoprecipitation and affinity-binding studies revealed that Rab23 exists in a complex with Kif17 and importin β2 (the putative Kif17 ciliary import carrier), implying that Kif17 needs to bind to regulatory proteins like Rab23 for its ciliary transport. Although a ciliary-cytoplasmic gradient of nuclear Ran is necessary to regulate the ciliary transport of Kif17, Rab23 and Ran appear to have differing roles in regulating the ciliary entry of Kif17. Our findings have uncovered a hitherto unknown effector of Rab23 and demonstrate how Rab23 could mediate the transport of Kif17 to the primary cilium.

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Section: Discussion Localization Of Rab23 At the Primary Ciliumsupporting

confidence: 54%

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

Lim

Tang

2015

Journal of Cell Science

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“…The small GTPase Rab27a is anchored into the melanosome membrane via lipophilic geranylgeranyl groups that are added post-translationally (27). An important feature of Rab proteins is their cycle of association with membranes in the GTP state and their dissociation from membranes in the GDP state (27).…”

mentioning

confidence: 99%

“…An important feature of Rab proteins is their cycle of association with membranes in the GTP state and their dissociation from membranes in the GDP state (27). A tripartite complex of myoVa, Mlph, and green fluorescent protein (GFP)-tagged Rab27a-GTP has been shown to move processively on actin in vitro, providing proof of principle that a transport complex can be reconstituted from these three proteins (28).…”

mentioning

confidence: 99%

More Than Just a Cargo Adapter, Melanophilin Prolongs and Slows Processive Runs of Myosin Va

Sckolnick

Krementsova

Warshaw

et al. 2013

Journal of Biological Chemistry

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Background: Melanophilin links myosin Va to Rab27a-melanosomes, a cargo it transports along actin tracks. Results: Melanophilin recruits more myosin Va motors to actin, slows their speed, and increases their processive run length. Conclusion:The actin binding domain of melanophilin acts as a tether to enhance processive runs. Significance: Proteins that link motors to cargo can enhance motor properties in ways that are favorable for their biological role.

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“…Rab small GTPases family proteins are considered key regulators of intracellular membrane trafficking and their deregulation is involved in multiple diseases, including cancer [15][16][17][18][19][20]. Alterations in membrane trafficking and the secretory pathway could modify cell polarity and membrane receptor distribution [21].…”

Section: Introductionmentioning

confidence: 99%

HighRAB25expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

et al. 2013

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Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment.

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Posttranslational modifications of Rab GTPases help their insertion into membranes

Cited by 9 publications

References 26 publications

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

More Than Just a Cargo Adapter, Melanophilin Prolongs and Slows Processive Runs of Myosin Va

HighRAB25expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

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