Functional diversification across yeast lineages of the nucleus-vacuole junction forming protein Nvj1

Kramer, F.; Millen, J.; Goldfarb, A. M.; Farre, J.-C.; Wolters, J. F.; Rokas, A.; Hittinger, C. T.; Subramani, S.; Fay, J. C.; Thumm, M.; Goldfarb, D. S.

doi:10.64898/2026.09.05.749613

bioRxiv · 10.64898/2026.09.05.749613

Functional diversification across yeast lineages of the nucleus-vacuole junction forming protein Nvj1

Kramer, F.·Millen, J.·Goldfarb, A. M.·Farre, J.-C.·Wolters, J. F.·Rokas, A.·Hittinger, C. T.·Subramani, S.·Fay, J. C.·Thumm, M.·Goldfarb, D. S.

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Abstract

Nucleus-vacuole junctions (NVJs) in Saccharomyces cerevisiae serve as an inter-organellar hub for multiple cell processes, including lipid transport and biosynthesis, an intra-nuclear quality control mechanism, and piecemeal microautophagy of the nucleus. NVJs are formed by complexes between Vac8 in the vacuole membrane and Nvj1 in the nuclear envelope. Nvj1 also links the inner and outer nuclear membranes across the perinuclear lumen. Orthologs of Nvj1 had previously only been found in yeasts of the order Saccharomycetales, raising the possibility that NVJs are restricted to this clade. Using homology and synteny, we discovered scores of novel Nvj1 orthologs across 200 million years of evolution within the subphylum Saccharomycotina. Not all orthologs mediate NVJ formation when expressed in S. cerevisiae, and some lack a sequence motif necessary for this function. Furthermore, the sequence motif required for binding the oxysterol binding protein Osh1 and an associated novel sequence motif, both found only in the order Saccharomycetales, were independently lost in three different lineages. This collection suggests specific opportunities to explore evolutionary and functional adaptations of Nvj1s in ecologically and physiologically diverse yeasts.

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Kramer, F., Millen, J., Goldfarb, A. M., Farre, J.-C., Wolters, J. F., Rokas, A., Hittinger, C. T., Subramani, S., Fay, J. C., Thumm, M., Goldfarb, D. S.. 2026-09-10. Functional diversification across yeast lineages of the nucleus-vacuole junction forming protein Nvj1. https://doi.org/10.64898/2026.09.05.749613

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