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J Cell Sci. 2019 Jan 16;132(2). pii: jcs224428. doi: 10.1242/jcs.224428.

RABL2 positively controls localization of GPCRs in mammalian primary cilia.

Author information

1
Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
2
Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno, Osaka, 545-8585, Japan.
3
Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan kobayt@bs.naist.jp.

Abstract

The primary cilium, a solitary protrusion from most mammalian cells, functions as a cell sensor by receiving extracellular signals through receptors and channels accumulated in the organelle. Certain G-protein-coupled receptors (GPCRs) specifically localize to the membrane compartment of primary cilia. To gain insight into the mechanisms that regulate ciliary GPCR sorting, we investigated the atypical small GTPase RAB-like 2 (RABL2; herein referring to the near-identical human paralogs RABL2A and RABL2B). RABL2 recruitment to the mother centriole is dependent on the distal appendage proteins CEP164 and CEP83. We found that silencing of RABL2 causes mis-targeting of ciliary GPCRs, GPR161 and HTR6, whereas overexpression of RABL2 resulted in accumulation of these receptors in the organelle. Ablation of CEP19 and the intraflagellar transport B (IFT-B) complex, which interact with RABL2, also leads to mis-localization of GPR161. RABL2 controls localization of GPR161 independently of TULP3, which promotes entry of ciliary GPCRs. We further demonstrate that RABL2 physically associates with ciliary GPCRs. Taken together, these studies suggest that RABL2 plays an important role in trafficking of ciliary GPCRs at the ciliary base in mammalian cells.

KEYWORDS:

GPCR; Primary cilia; RABL2; Trafficking

PMID:
30578315
DOI:
10.1242/jcs.224428

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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