The ER-Localized Protein DFCP1 Modulates ER-Lipid Droplet Contact Formation

Li, Dongfang; Zhao, Yan; Li, Di; Zhao, Hongyu; Huang, Jie; Miao, Guangyan; Feng, Du; Liu, Pingsheng; Liu, Dong; Zhang, Hong

doi:10.1016/j.celrep.2019.03.025

Cited by 90 publications

(108 citation statements)

References 30 publications

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“…Active GTP‐Rab18 on LD mediates LD‐ER contact via its interaction with the ER‐bound NRZ tethering complex and their associated SNAREs (Xu et al, ). More recently, DFCP1 has been reported to be a Rab18 effector and promotes LD expansion (Li et al, ). However, we observed a change in LD morphology in the DFCP1‐KO MEF cells with smaller but more LDs, TAG accumulation remains unaffected in our study.…”

Section: Discussionmentioning

confidence: 99%

“…The antibody against GFP (rabbit, sc‐8334) was purchased from Santa Cruz Biotechnology. The antibody against DFCP1 (rabbit, ABclonal A7527) was a kind gift from Prof Hong Zhang (Li et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…293T, HepG2, HeLa, COS‐7, NRK, NRK‐GFP‐DFCP1 (Ma et al, ), wild‐type or Rab18‐null 3T3‐L1 cells (Xu et al, ) and wild type or DFCP1‐null MEF cells (Li et al, ) were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (Gibco), 2 mM l ‐glutamine, 100 μg/mL streptomycin, and 100 U/mL penicillin at 37°C in a humidified incubator containing 5% CO 2 . Electroporation of plasmid DNA into 3T3‐L1 pre‐adipocytes, NRK or HepG2 cells was performed using an Amaxa Nucleofector II (Lonza) with the respective program.…”

Section: Methodsmentioning

confidence: 99%

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DFCP1 associates with lipid droplets

Gao

Sheng

Yang

et al. 2019

Cell Biology International

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Double FYVE-containing protein 1 (DFCP1) is ubiquitously expressed, participates in intracellular membrane trafficking and labels omegasomes through specific interactions with phosphatidylinositol-3-phosphate (PI3P). Previous studies showed that subcellular DFCP1 proteins display multi-organelle localization, including in the endoplasmic reticulum (ER), Golgi apparatus and mitochondria. However, its localization and function on lipid droplets (LDs) remain unclear. Here, we demonstrate that DFCP1 localizes to the LD upon oleic acid incubation. The ER-targeted domain of DFCP1 is indispensable for its LD localization, which is further enhanced by double FYVE domains. Inhibition of PI3P binding at the FYVE domain through wortmannin treatment or double mutation at C654S and C770S have no effect on DFCP1's LD localization. These show that the mechanisms for DFCP1 targeting the omegasome and LDs are different. DFCP1 deficiency in MEF cells causes an increase in LD number and reduces LD size. Interestingly, DFCP1 interacts with GTP-bound Rab18, an LDassociated protein. Taken together, our work demonstrates the dynamic localization of DFCP1 is regulated by nutritional status in response to cellular metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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DFCP1 associates with lipid droplets

Gao

Sheng

Yang

et al. 2019

Cell Biology International

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“…Rab18 has been shown to mediate the interaction between LD and ER [26,33]. Li et al also reveals that the DFCP1-Rab18 complex is involved in tethering the ER-LD contact for LD expansion and initial LD growth [36,37]. Another possible mechanism is that Rab18 specifically binds to the ER-associated NAG-RINT1-ZW10 tethering complex [38].…”

Section: Introductionmentioning

confidence: 99%

Rab18 Binds PLIN2 and ACSL3 to Mediate Lipid Droplet Dynamics

Deng

Zhou

Mirza

et al. 2020

Preprint

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Rab18 has been linked to lipid metabolism and metabolic diseases in different model systems, but the mechanism of Rab18-mediated lipid droplet (LD) dynamics in muscle cells remains elusive. Here, we report that Rab18 plays an essential role in oleic acid (OA)-induced LD growth and formation in mouse myoblast cell line C2C12. Rab18 was translocated from endoplasmic reticulum (ER) to LDs during the LD growth induced by OA in C2C12 cells, which was directly regulated by perilipin 2 (PLIN2), a LD resident protein. LD-associated Rab18 bound with the C terminus of PLIN2, and the LD localization of Rab18 was diminished after PLIN2 deletion. Moreover, loss of function of Rab18 led to less triacylglycerol (TAG) accumulation and fewer but larger LD formation. In contrast, expression of wild type Rab18 and a constitutively active Rab18 (Q67L) mutant resulted in elevated TAG content and LD number. Furthermore, LD-associated Rab18 interacted with acyl-CoA synthetase long-chain family member 3 (ACSL3) and in turn, promoted the LD localization of ACSL3, which may play an important role in the accumulation of TAG induced by OA. These data showed that Rab18 was recruited to LD after OA treatment, and formed a complex with PLIN2 and ACSL3, which contributes to TAG accumulating and LD growth.

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“…The ER is a large, continuous, single-membrane-bound organelle found in eukaryotic cells, which forms dynamic contacts with other membrane-bound organelles, such as LDs (Li et al, 2019;Nguyen and Olzmann, 2019), mitochondria (Vance, 2014;Rodriguez-Arribas et al, 2017), Golgi (Salo et al, 2016), endosomes (Friedman et al, 2013;Dong et al, 2016), and IMs (Zhao et al, 2017) to maintain normal cellular processes. Communication between organelles at membrane contact sites plays important roles in cellular biological processes.…”

Section: Introductionmentioning

confidence: 99%

Roles of VMP1 in Autophagy and ER–Membrane Contact: Potential Implications in Neurodegenerative Disorders

Wang

Kou

2020

Front. Mol. Neurosci.

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Cellular communication processes are highly dynamic and mediated, at least in part, by contacts between various membrane structures. The endoplasmic reticulum (ER), the major biosynthetic organelle of the cell, establishes an extensive network with other membrane structures to regulate the transport of intracellular molecules. Vacuole membrane protein 1 (VMP1), an ER-localized metazoan-specific protein, plays important roles in the formation of autophagosomes and communication between the ER and other organelles, including mitochondria, autophagosome precursor membranes, Golgi, lipid droplets, and endosomes. Increasing evidence has indicated that autophagy and ER-membrane communication at membrane contact sites are closely related to neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. In this review, we summarize the roles of VMP1 in autophagy and ER-membrane contacts and discuss their potential implications in neurodegenerative disorders.

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The ER-Localized Protein DFCP1 Modulates ER-Lipid Droplet Contact Formation

Cited by 90 publications

References 30 publications

DFCP1 associates with lipid droplets

DFCP1 associates with lipid droplets

Rab18 Binds PLIN2 and ACSL3 to Mediate Lipid Droplet Dynamics

Roles of VMP1 in Autophagy and ER–Membrane Contact: Potential Implications in Neurodegenerative Disorders

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