Lam6 Regulates the Extent of Contacts between Organelles

Elbaz‐Alon, Yael; Eisenberg-Bord, Michal; Shinder, Vera; Stiller, Sebastian B.; Shimoni, Eyal; Wiedemann, Nils; Geiger, Tamar; Schuldiner, Maya

doi:10.1016/j.celrep.2015.06.022

Cited by 184 publications

(224 citation statements)

References 19 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…Consistent with the localization of Ltc1 at ER-mitochondria contact sites, two other research groups identified Ltc1 as an interactor with the ERMES complex based on proteomic analyses (118,119). The absence of Ltc1 alone did not impair growth on fermentable or nonfermentable carbon sources or affect mitochondrial morphology or assembly of the ERMES complex; however, it did aggravate the growth defect of ERMES mutants, suggesting that Ltc1 and ERMES fulfill different roles toward mitochondrial functionality (118,119).…”

Section: Multiple Roles For Ermes In Mitochondrial Biologymentioning

confidence: 56%

“…The absence of Ltc1 alone did not impair growth on fermentable or nonfermentable carbon sources or affect mitochondrial morphology or assembly of the ERMES complex; however, it did aggravate the growth defect of ERMES mutants, suggesting that Ltc1 and ERMES fulfill different roles toward mitochondrial functionality (118,119). Murley et al (118) showed that the majority of Ltc1 localized at ER-mitochondria MCSs with about half colocalizing with ERMES foci.…”

Section: Multiple Roles For Ermes In Mitochondrial Biologymentioning

confidence: 99%

“…Interestingly, a minor fraction of Ltc1 also localized to vCLAMP (119), in addition to ERMES and NVJ, and overexpression of Ltc1 led to the expansion of all of these MCSs. Almost all the mitochondria were in contact with the ER with 60% of their circumference covered with ER when Ltc1 was overexpressed.…”

Section: Multiple Roles For Ermes In Mitochondrial Biologymentioning

confidence: 99%

See 2 more Smart Citations

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Fernández-Murray

McMaster

2016

Journal of Lipid Research

View full text Add to dashboard Cite

high throughput analyses, makes this yeast a powerful organism to unveil the intricacies of this field. The yeast S. cerevisiae has played a foundational role in the field of molecular and cellular biology of lipids, including the identification of membrane contact sites (MCSs) and how they link lipid metabolism with organelle dynamics. We present advances in two topics where extensive and outstanding contributions have recently been made where their relevance transcends the yeast lipid field. We first review new information about the phosphatidic acid (PA) phosphatase, Pah1, the yeast homolog of human lipin, and its role in directing lipid flux into membrane synthesis or storage. We review the contribution of Pah1 to lipid droplet (LD) formation and its interaction with the seipin complex, Fld1/Ldb16, to regulate endoplasmic reticulum (ER)-LD contact site dynamics. Second, we recapitulate recent developments revealing MCS connections between the ER and mitochondria with other cellular compartments, and how these intersect with the maintenance of lipid homeostasis. Furthermore, we explore MCS redundancies that allow cells to cope with changing metabolic demand. PA METABOLISM CO-COORDINATES MEMBRANE AND LD SYNTHESISPA is the common precursor for the synthesis of membrane phospholipids (PLs) and the major component of The pervasive importance of lipids in cell biology has become evident. From structural roles defining cellular compartments and surfaces with specific biological properties to functional roles in signal transduction processes and modulation of regulatory networks, the involvement of lipids in varied cellular functions is well-established. Concurrently, we have gained a broad understanding about the repertoire of proteins involved in synthesis, degradation, transport, and sensing of lipids, as well as the regulatory mechanisms that interconnect lipid metabolism with other cellular processes. The amenability of Saccharomyces cerevisiae to classical approaches of molecular genetics, and toThe work on the science described in this review was supported by a Discovery Grant from the Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada to C.R.M. Manuscript received 19 July 2016 and in revised form 6 August 2016. Published, JLR Papers in Press, August 12, 2016 DOI 10.1194 Lipid synthesis and membrane contact sites: a crossroads for cellular physiology Abbreviations: cER, cortical endoplasmic reticulum; ChiMERA, construct helping in mitochondria-endoplasmic reticulum association; CL, cardiolipin; DAG, diacylglycerol; EMC, endoplasmic reticulum membrane protein complex; ER, endoplasmic reticulum; ERMES, endoplasmic reticulum-mitochondria encounter structure; HOPS, homotypic fusion and vacuole protein sorting; Lam, lipid transfer protein anchored at a membrane contact site; LD, lipid droplet; Ltc, lipid transfer at contact site; LTP, lipid transfer protein; Mcp, maintenance of mitochondrial morphology 10 complementing protein; M...

show abstract

Section: Multiple Roles For Ermes In Mitochondrial Biologymentioning

confidence: 56%

Section: Multiple Roles For Ermes In Mitochondrial Biologymentioning

confidence: 99%

See 1 more Smart Citation

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Fernández-Murray

McMaster

2016

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Ltc1p (also known as Lam6p), an ER integral membrane protein, is localized to NVJ via its binding to Vac8p (31,33). Another integral ER membrane protein, Mdm1p, binds vacuolar phosphatidylinositol-3-phosphate through its PX domain, forming NVJs (32).…”

Section: Discussionmentioning

confidence: 99%

Mechanistic insight into the nucleus–vacuole junction based on the Vac8p–Nvj1p crystal structure

Jeong

Park

Kim

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Formation of the nucleus-vacuole junction (NVJ) is mediated by direct interaction between the vacuolar protein Vac8p and the outer nuclear endoplasmic reticulum membrane protein Nvj1p. Herein we report the crystal structure of Vac8p bound to Nvj1p at 2.4-Å resolution. Vac8p comprises a flexibly connected N-terminal H1 helix followed by 12 armadillo repeats (ARMs) that form a right-handed superhelical structure. The extended 80-Å-long loop of Nvj1p specifically binds the highly conserved inner groove formed from ARM1−12 of Vac8p. Disruption of the Nvj1p-Vac8p interaction results in the loss of tight NVJs, which impairs piecemeal microautophagy of the nucleus in Saccharomyces cerevisiae. Vac8p cationic triad (Arg276, Arg317, and Arg359) motifs interacting with Nvj1p are also critical to the recognition of Atg13p, a key component of the cytoplasm-to-vacuole targeting (CVT) pathway, indicating competitive binding to Vac8p. Indeed, mutation of the cationic triad abolishes CVT of Ape1p in vivo. Combined with biochemical data, the crystal structure reveals a Vac8p homodimer formed from ARM1, and this self-association, likely regulated by the flexible H1 helix and the C terminus of Nvj1p, is critical for Vac8p cellular functions. M embrane contact sites (MCSs) between subcellular compartments play pivotal roles in cellular processes such as cooperative lipid biosynthesis, ion homeostasis, and interorganellar trafficking of molecules in eukaryotic cells (1-3). MCSs are physically formed through dynamic and direct interactions between proteins that are located in two distinct subcompartments. The nucleus-vacuole junction (NVJ), one of the best-characterized MCSs, is a physical contact site between perinuclear and vacuolar membranes and mediates essential cellular processes such as piecemeal microautophagy of the nucleus (PMN) and lipid biosynthesis in yeast (4, 5). PMN is a selective autophagic recycling process stimulated by carbon or nitrogen starvation through the target of rapamycin signaling pathway in Saccharomyces cerevisiae. Upon nutrient starvation, the region of the nucleus in the vicinity of NVJs invaginates into the vacuolar lumen and forms a bleb-like structure, which is released as a vesicle and eventually degraded by vacuolar hydrolases (5, 6). Because PMN occurs at the NVJ sites, their formation is essential for the initiation of the PMN process (7). NVJs are also involved in lipid metabolism by recruiting the two lipid-modifying enzymes, oxystereol-binding proteins homology (Osh1p) involved in nonvesicular lipid trafficking and the enoyl-CoA reductase Tsc13p that mediates the synthesis of verylong-chain fatty acids (8-11).Previous studies revealed that NVJs are generated by forming tight interactions between Vac8p, a vacuolar membrane protein, and Nvj1p, a nuclear membrane protein (12). Vac8p was initially found as a key player in vacuole inheritance by cooperating with Vac17p, actin, profilin, and Myo2p (13). In addition, Vac8p has a crucial role in mediating the processing of aminopeptidase I through in...

show abstract

“…Mammalian MAMs are formed by protein tethers, similar to the tetrameric tethering complexes in fungi known as ER-mitochondria encounter structures (ERMES) (Kornmann et al, 2009). However, of the more than 30 proteins involved in vertebrate MAM function, only two of them, GRAMD1A, which corresponds to yeast Lam6p, and MIRO (also known as RHOT1), which corresponds to yeast Gem1p, are conserved in ERMES (Kornmann et al, 2011;Elbaz-Alon et al, 2015). This increased complexity of animal MAMs suggests they acquired new roles beyond those controlled by ERMES (HerreraCruz and Simmen, 2017).…”

Section: Introductionmentioning

confidence: 99%

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Thomas

Aslan

Thomas

et al. 2017

Journal of Cell Science

View full text Add to dashboard Cite

Vertebrate proteins that fulfill multiple and seemingly disparate functions are increasingly recognized as vital solutions to maintaining homeostasis in the face of the complex cell and tissue physiology of higher metazoans. However, the molecular adaptations that underpin this increased functionality remain elusive. In this Commentary, we review the PACS proteins -which first appeared in lower metazoans as protein traffic modulators and evolved in vertebrates to integrate cytoplasmic protein traffic and interorganellar communication with nuclear gene expression -as examples of protein adaptation 'caught in the act'. Vertebrate PACS-1 and PACS-2 increased their functional density and roles as metabolic switches by acquiring phosphorylation sites and nuclear trafficking signals within disordered regions of the proteins. These findings illustrate one mechanism by which vertebrates accommodate their complex cell physiology with a limited set of proteins. We will also highlight how pathogenic viruses exploit the PACS sorting pathways as well as recent studies on PACS genes with mutations or altered expression that result in diverse diseases. These discoveries suggest that investigation of the evolving PACS protein family provides a rich opportunity for insight into vertebrate cell and organ homeostasis.

show abstract

Lam6 Regulates the Extent of Contacts between Organelles

Cited by 184 publications

References 19 publications

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Mechanistic insight into the nucleus–vacuole junction based on the Vac8p–Nvj1p crystal structure

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Contact Info

Product

Resources

About