Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway

Ganga, Anil Kumar; Kennedy, Margaret C.; Oguchi, Mai E.; Gray, Shawn; Oliver, Kendall E.; Knight, Tracy A.; Cruz, Enrique M. De La; Homma, Yuta; Fukuda, M.; Breslow, David K.

doi:10.1016/j.cub.2021.04.075

Cited by 32 publications

(28 citation statements)

References 61 publications

(70 reference statements)

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“…It is unclear why eGFP-KIF13B localizes to cilia in hTERT-RPE1 cells and not IMCD3 cells, but the former possess a deep ciliary pocket whereas the latter do not (Ghossoub et al, 2011), which might influence the ability of KIF13B to enter cilia. Similarly, RAB34 was recently shown to function specifically at cilia in cells with a ciliary pocket (Ganga et al, 2021, Stuck et al, 2021).…”

Section: Resultsmentioning

confidence: 88%

Transient accumulation and bidirectional movement of KIF13B in primary cilia

Juhl

Anvarian

Berges

et al. 2021

Preprint

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Primary cilia are microtubule-based sensory organelles whose assembly and function rely on the conserved bidirectional intraflagellar transport (IFT) system, which is powered by anterograde kinesin-2 and retrograde cytoplasmic dynein 2 motors. Nematodes additionally employ a male-specific kinesin-3 motor, KLP-6, which regulates ciliary content and function by promoting release of bioactive extracellular vesicles (EVs) from cilia. Here we show by live cell imaging that a KLP-6 homolog, KIF13B, undergoes bursts of bidirectional movement within primary cilia of cultured mammalian cells at 0.64 ± 0.07 μm/s in the anterograde direction and at 0.39 ± 0.06 μm/s in the retrograde direction, reminiscent of conventional IFT. In addition, we found that KIF13B undergoes EV-like release from the ciliary tip whereas a ciliary membrane marker, SMO-tRFP, remains stably associated with cilia during such EV release. Our results suggest that KIF13B, similar to KLP-6, regulates ciliary membrane content by promoting ciliary EV release, possibly in coordination with conventional IFT.

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Section: Resultsmentioning

confidence: 88%

Transient accumulation and bidirectional movement of KIF13B in primary cilia

Juhl

Anvarian

Berges

et al. 2021

Preprint

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“…To begin with, cilia formation, which involves assembly and extensive tubulation of membrane‐bound vesicles around the mother centriole (Sorokin, 1962), needs phosphatidylinositol‐3‐phosphate (PI(3)P) (Franco et al, 2014). Although it is still unclear how lipid dynamics facilitate the formation and flattening of lipid vesicles, the PI(3)P enrichment at the periciliary vesicle indicates that the phosphoinositide formation could recruit the small GTPase Rab8 and its effectors, such as the Bin‐Amphiphysin‐RVS (BAR) domain‐containing proteins PASCIN1/2 and EHD1/3 (Insinna et al, 2019; Q. Lu, Insinna, et al, 2015) and Rab34 (Ganga et al, 2021; Stuck et al, 2021). The BAR‐domain proteins are recruited to the membrane rich in negatively charged lipid head groups such as the phosphatidylcholine (PC), phosphatidylserine (PS) and phosphoinositides (Nishimura et al, 2018) through the small GTPases Rab8 and Rab11, which play a significant role in the cilia assembly (Westlake et al, 2011; Yoshimura et al, 2007).…”

Section: Ciliary Lipids—composition and Local Modificationmentioning

confidence: 99%

“…The BAR-domain proteins are recruited to the membrane rich in negatively charged lipid head groups such as the phosphatidylcholine (PC), phosphatidylserine (PS) and phosphoinositides (Nishimura et al, 2018) through the small GTPases Rab8 and Rab11, which play a significant role in the cilia assembly (Westlake et al, 2011;Yoshimura et al, 2007). A recent study further implicated Rab34 in flattening the ciliary vesicles once they associate with the distal appendage (Ganga et al, 2021;Stuck et al, 2021).…”

Section: Phosphoinositidesmentioning

confidence: 99%

Ciliary membrane, localised lipid modification and cilia function

Dutta

Ray

2022

Journal Cellular Physiology

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Cilium, a tiny microtubule‐based cellular appendage critical for cell signalling and physiology, displays a large variety of receptors. The composition and turnover of ciliary lipids and receptors determine cell behaviour. Due to the exclusion of ribosomal machinery and limited membrane area, a cilium needs adaptive logistics to actively reconstitute the lipid and receptor compositions during development and differentiation. How is this dynamicity generated? Here, we examine whether, along with the Intraflagellar‐Transport, targeted changes in sector‐wise lipid composition could control the receptor localisation and functions in the cilia. We discuss how an interplay between ciliary lipid composition, localised lipid modification, and receptor function could contribute to cilia growth and signalling. We argue that lipid modification at the cell‐cilium interface could generate an added thrust for a selective exchange of membrane lipids and the transmembrane and membrane‐associated proteins.

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“…Presently, more than 60 RABs have been identified in humans (Anand et al, 2020). Deregulation of RABs has been reported in several diseases, including various cancers (Sun et al, 2018;Ganga et al, 2021). They function either as an oncogene or tumor suppressors depending on cancer types.…”

Section: Introductionmentioning

confidence: 99%

The Role of RAB GTPases and Its Potential in Predicting Immunotherapy Response and Prognosis in Colorectal Cancer

et al. 2022

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide, in which aberrant activation of the RAS signaling pathway appears frequently. RAB proteins (RABs) are the largest Ras small GTPases superfamily that regulates intracellular membrane trafficking pathways. The dysregulation of RABs have been found in various diseases including cancers. Compared with other members of Ras families, the roles of RABs in colorectal cancer are less well understood.Methods: We analyzed the differential expression and clinicopathological association of RABs in CRC using RNA sequencing and genotyping datasets from TCGA samples. Moreover, the biological function of RAB17 and RAB34 were investigated in CRC cell lines and patient samples.Results: Of the 62 RABs we analyzed in CRC, seven (RAB10, RAB11A, RAB15, RAB17, RAB19, RAB20, and RAB25) were significantly upregulated, while six (RAB6B, RAB9B, RAB12, RAB23, RAB31, and RAB34) were significantly downregulated in tumor tissues as compared to normal. We found that the upregulated-RABs, which were highly expressed in metabolic activated CRC subtype (CMS3), are associated with cell cycle related pathways enrichment and positively correlated with the mismatch repair (MMR) genes in CRC, implying their role in regulating cell metabolism and tumor growth. While, high expression of the downregulated-RABs were significantly associated with poor prognostic CRC mesenchymal subtypes (CMS4), immune checkpoint genes, and tumor infiltrating immune cells, indicating their role in predicting prognosis and immunotherapy efficacy. Interestingly, though RAB34 mRNA is downregulated in CRC, its high expression is significantly associated with poor prognosis. In vitro experiments showed that RAB17 overexpression can promote cell proliferation via cell cycle regulation. While, RAB34 overexpression can promote cell migration and invasion and is associated with PD-L1/PD-L2 expression increase in CRC cells.Conclusions: Our study showed that RABs may play important roles in regulating cell cycle and immune-related pathways, therefore might be potential biomarkers in predicting prognosis and immunotherapy response in CRC.

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Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway

Cited by 32 publications

References 61 publications

Transient accumulation and bidirectional movement of KIF13B in primary cilia

Transient accumulation and bidirectional movement of KIF13B in primary cilia

Ciliary membrane, localised lipid modification and cilia function

The Role of RAB GTPases and Its Potential in Predicting Immunotherapy Response and Prognosis in Colorectal Cancer

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