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Wälte, M.

Publications and source records attributed to Wälte, M..

3 recordsLinked to original sources

Role of Pex31 in metabolic adaptation of the nucleus vacuole junction NVJ

The nucleus vacuole junction NVJ in yeast is a multifunctional contact site between the nuclear ER membrane and the vacuole with diverse roles in lipid metabolism, transfer and storage. Adaptation of NVJ functions to metabolic cues is mediated by a striking remodeling of the size and the proteome of the contact site, but the extent and the molecular determinants of this plasticity are not fully understood. Using microscopy-based screens, we monitored NVJ remodeling in response to glucose availability. We identified Pex31, Nsg1, Nsg2, Shr5, and Tcb1 as NVJ residents. Glucose starvation typically results in an expansion of the NVJ size and proteome. Pex31 shows an atypical behavior, being specifically enriched at the NVJ at high glucose conditions. Loss of Pex31 uncouples NVJ remodeling from glucose availability, resulting in recruitment of glucose starvation-specific residents and NVJ expansion at glucose replete conditions. Moreover, PEX31 deletion results in alterations of sterol ester storage and a remodeling of vacuolar membranes that phenocopy glucose starvation responses. We conclude that Pex31 has a role in metabolic adaptation of the NVJ. SUMMARY STATEMENTUsing microscopy-based screens in yeast, we identified Pex31, Nsg1, Nsg2, Shr5 and Tcb1 as residents of the nucleus vacuole junction NVJ. Pex31 has a role in NVJ adaptation to glucose availability.

cell biology↗

The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility

Organelle motility enables strategic cellular reorganizations. In yeast, this process depends on the actin cytoskeleton, type V myosin motor proteins, and organelle-specific myosin adaptor proteins. While the myosin adaptors for most organelles are known, the coupling of myosin to lipid droplets (LDs), the cellular lipid storage organelles, remained enigmatic. Using genome-wide screening, we identified Ldm1 (Lipid Droplet Motility 1/Yer085c) as a myosin adaptor. Ldm1 binds to the globular tail domain of the myosin Myo2 and to the LD surface protein Ldo16 to enable actin-dependent LD motility. Ldo16 has additional roles in LD contact sites to the vacuole and the ER, suggesting a coordination of LD motility and organelle tethering. Ldm1 has a second role in mitochondrial transport and elevated Ldm1 levels rescue defects of the mitochondrial Myo2-adaptors Mmr1/Ypt11. Our work identifies the molecular machinery for LD motility and contributes to a comprehensive understanding of acto-myosin-based cellular reorganization.

cell biology↗

A metabolically controlled contact site between lipid droplets and vacuoles

The lipid droplet (LD) organization proteins Ldo16 and Ldo45 affect multiple aspects of LD biology in yeast. They are linked to the LD biogenesis machinery seipin, and their loss causes defects in LD positioning, protein targeting, and breakdown. However, their molecular roles remained enigmatic. Here we report that Ldo16/45 form a tether-complex with Vac8 for creation of vacuole lipid droplet (vCLIP) contact sites, which can form in the absence of seipin. The phosphatidylinositol transfer protein Pdr16 is a further vCLIP-resident recruited by Ldo45. While only an LD-subpopulation is engaged in vCLIPs at glucose-replete conditions, nutrient stress results in vCLIP expansion, and vCLIP defects impair lipophagy upon prolonged starvation. In summary, Ldo16/45 are multifunctional proteins that orchestrate formation of a metabolically-regulated contact site. Our studies suggest an unexpected link between LD biogenesis and breakdown, and open the door to a deeper understanding of how lipid homeostasis is maintained during metabolic challenges.

cell biology↗