Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane

Ozeki, Shintaro; Cheng, Jinglei; Tauchi-Sato, Kumi; Hatano, Naoya; Taniguchi, Hiroyuki; Fujimoto, Toyoshi

doi:10.1242/jcs.02401

Cited by 324 publications

(360 citation statements)

References 45 publications

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“…In particular, several members of the RAB family of small GTPases have been shown to decorate the surface of LDs (Brasaemle et al 2004, Murphy et al 2009), yet the precise function of most RAB proteins expressed in adipocytes remains unknown. Among those best documented is RAB18, which was first shown to associate with the surface of LDs in 3T3-L1 adipocytes in response to b-adrenergic stimulation and was therefore proposed to be involved in the release of lipids from LDs (Brasaemle et al 2004, Martin et al 2005, Ozeki et al 2005. Consistent with these early studies, we recently demonstrated that RAB18 overexpression increased basal lipolysis and RAB18 silencing-impaired forskolin-stimulated lipolysis in 3T3-L1 cells (Pulido et al 2011).…”

Section: Introductionsupporting

confidence: 77%

Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue

Pulido

Almabouada

Díaz‐Ruiz

et al. 2012

Journal of Molecular Endocrinology

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There is increasing evidence that proteins associated with lipid droplets (LDs) play a key role in the coordination of lipid storage and mobilization in adipocytes. The small GTPase, RAB18, has been recently identified as a novel component of the protein coat of LDs and proposed to play a role in both b-adrenergic stimulation of lipolysis and insulin-induced lipogenesis in 3T3-L1 adipocytes. In order to better understand the role of Rab18 in the regulation of lipid metabolism in adipocytes, we evaluated the effects of age, fat location, metabolic status, and hormonal milieu on Rab18 expression in rodent white adipose tissue (WAT). Rab18 mRNA was undetectable at postnatal day 15 (P15), but reached adult levels by P45, in both male and female rats. In adult rats, Rab18 immunolocalized around LDs, as well as within the cytoplasm of mature adipocytes. A weak Rab18 signal was also detected in the stromal-vascular fraction of WAT. In mice, fasting significantly increased, though with a distinct time-course pattern, Rab18 mRNA and protein levels in visceral and subcutaneous WAT. The expression of Rab18 was also increased in visceral and subcutaneous WAT of obese mice (diet-induced, ob/ob, and New Zealand obese mice) compared with lean controls. Rab18 expression in rats was unaltered by castration, adrenalectomy, or GH deficiency but was increased by hypophysectomy, as well as hypothyroidism. When viewed together, our results suggest the participation of Rab18 in the regulation of lipid processing in adipose tissue under both normal and pathological conditions.

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Section: Introductionsupporting

confidence: 77%

Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue

Pulido

Almabouada

Díaz‐Ruiz

et al. 2012

Journal of Molecular Endocrinology

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“…Instead, LD‐linked proteins are found to associate through alternative mechanisms (i.e., lipid modifications, hairpin loops, or amphipathic helices4). Numerous proteomic studies have shown that a significant number of Rab family members are consistently associated with the LD monolayer,5, 6, 40, 41, 42, 43, 44 likely through interactions occurring though C‐terminal prenylation sites. Among the Rabs, Rab7 and Rab18 appear to be especially prominent on the LD, as evidenced by their repeated presence in the diverse proteomic analyses listed above.…”

Section: Discussionmentioning

confidence: 99%

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Schulze¹,

Rasineni

Weller³

et al. 2017

Hepatology Communications

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Alcohol consumption is a well‐established risk factor for the onset and progression of fatty liver disease. An estimated 90% of heavy drinkers are thought to develop significant liver steatosis. For these reasons, an increased understanding of the molecular basis for alcohol‐induced hepatic steatosis is important. It has become clear that autophagy, a catabolic process of intracellular degradation and recycling, plays a key role in hepatic lipid metabolism. We have shown that Rab7, a small guanosine triphosphatase known to regulate membrane trafficking, acts as a key orchestrator of hepatocellular lipophagy, a selective form of autophagy in which lipid droplets (LDs) are specifically targeted for turnover by the autophagic machinery. Nutrient starvation results in Rab7 activation on the surface of the LD and lysosomal compartments, resulting in the mobilization of triglycerides stored within the LDs for energy production. Here, we examine whether the steatotic effects of alcohol exposure are a result of perturbations to the Rab7‐mediated lipophagic pathway. Rats chronically fed an ethanol‐containing diet accumulated significantly higher levels of fat in their hepatocytes. Interestingly, hepatocytes isolated from these ethanol‐fed rats contained juxtanuclear lysosomes that exhibited impaired motility. These changes are similar to those we observed in Rab7‐depleted hepatocytes. Consistent with these defects in the lysosomal compartment, we observed a marked 80% reduction in Rab7 activity in cultured hepatocytes as well as a complete block in starvation‐induced Rab7 activation in primary hepatocytes isolated from chronic ethanol‐fed animals. Conclusion: A mechanism is supported whereby ethanol exposure inhibits Rab7 activity, resulting in the impaired transport, targeting, and fusion of the autophagic machinery with LDs, leading to an accumulation of hepatocellular lipids and hepatic steatosis. (Hepatology Communications 2017;1:140‐152)

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“…We identified Rab1, 7, 8, 10, 11, and 18 in the C. elegans LD proteome. The small GTPase Rab18 localizes to LDs and promotes their close apposition to rough ER in human and mouse cells (2,31). Rab10 and Rab35 have been shown to positively regulate LD size in Drosophila S2 cells (32).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Study and Marker Protein Identification of Caenorhabditis elegans Lipid Droplets

Zhang

Liu

et al. 2012

Molecular & Cellular Proteomics

159

125

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Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane

Cited by 324 publications

References 45 publications

Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue

Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Proteomic Study and Marker Protein Identification of Caenorhabditis elegans Lipid Droplets

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