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Review
. 2020 Feb 28:11:136.
doi: 10.3389/fgene.2020.00136. eCollection 2020.

SUNny Ways: The Role of the SUN-Domain Protein Mps3 Bridging Yeast Nuclear Organization and Lipid Homeostasis

Maria Laura Sosa Ponce  1   2 , Sarah Moradi-Fard  1 , Vanina Zaremberg  2 , Jennifer A Cobb  1
Affiliations
Review

SUNny Ways: The Role of the SUN-Domain Protein Mps3 Bridging Yeast Nuclear Organization and Lipid Homeostasis

Maria Laura Sosa Ponce et al. Front Genet. .

Abstract

Mps3 is a SUN (Sad1-UNC-84) domain-containing protein that is located in the inner nuclear membrane (INM). Genetic screens with multiple Mps3 mutants have suggested that distinct regions of Mps3 function in relative isolation and underscore the broad involvement of Mps3 in multiple pathways including mitotic spindle formation, telomere maintenance, and lipid metabolism. These pathways have largely been characterized in isolation, without a holistic consideration for how key regulatory events within one pathway might impinge on other aspects of biology at the nuclear membrane. Mps3 is uniquely positioned to function in these multiple pathways as its N- terminus is in the nucleoplasm, where it is important for telomere anchoring at the nuclear periphery, and its C-terminus is in the lumen, where it has links with lipid metabolic processes. Emerging work suggests that the role of Mps3 in nuclear organization and lipid homeostasis are not independent, but more connected. For example, a failure in regulating Mps3 levels through the cell cycle leads to nuclear morphological abnormalities and loss of viability, suggesting a link between the N-terminal domain of Mps3 and nuclear envelope homeostasis. We will highlight work suggesting that Mps3 is pivotal factor in communicating events between the nucleus and the lipid bilayer.

Keywords: SUN-domain proteins; lipid metabolism; nuclear envelope; telomeres; transcription.

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Figures

Figure 1
Figure 1
Schematic of Mps3 domains. Mps3 consists of an N-terminal nucleoplasmic region (1–150 aa), a transmembrane domain (154–181 aa), a P-loop (187–194 aa), two coiled-coil domains (242–260 and 366–390) and a SUN domain (427–616). SUN domains typically associate with KASH domain proteins in the outer nuclear membrane after trimerization of the SUN-domain protein. Mps3 can be modified by acetylation, ubiquitination or phosphorylation.
Figure 2
Figure 2
Mps3 is at the crossroads of lipid metabolism and telomere organization. (A) Mps3 participates in tethering of telomeres through interactions with Sir4 and Est1. These interactions facilitate maintenance of telomere length, telomere clustering, and telomere silencing. The position of Mps3 in the nuclear membrane makes it a potential sensor to communicate changes in membrane composition to the nucleus, potentially affecting telomere regulation. Potential KASH-like binding partners of Mps3 like Scs2 (red), Sec20, and Csm4/Mps2 are indicated, as well as enzymes related to lipid metabolism mentioned in the text. DAG, diacylglycerol; PA, phosphatidic acid; PI, phosphatidylinositol; PS, phosphatidylserine; PLs, phospholipids; TAG, triacylglycerol. (B) Summary of the genetic interactions between mps3 mutants and genes involved in lipid biosynthesis regulation.
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