Phosphorylation of luminal region of the SUN-domain protein Mps3 promotes nuclear envelope localization during meiosis

Abstract

During meiosis, protein ensembles in the nuclear envelope (NE) containing SUN- and KASH-domain proteins, called linker nucleocytoskeleton and cytoskeleton (LINC) complex, promote the chromosome motion. Yeast SUN-domain protein, Mps3, forms multiple meiosis-specific ensembles on NE, which show dynamic localisation for chromosome motion; however, the mechanism by which these Mps3 ensembles are formed during meiosis remains largely unknown. Here, we showed that the cyclin-dependent protein kinase (CDK) and Dbf4-dependent Cdc7 protein kinase (DDK) regulate meiosis-specific dynamics of Mps3 on NE, particularly by mediating the resolution of Mps3 clusters and telomere clustering. We also found that the luminal region of Mps3 juxtaposed to the inner nuclear membrane is required for meiosis-specific localisation of Mps3 on NE. Negative charges introduced by meiosis-specific phosphorylation in the luminal region of Mps3 alter its interaction with negatively charged lipids by electric repulsion in reconstituted liposomes. Phospho-mimetic substitution in the luminal region suppresses the localisation of Mps3 via the inactivation of CDK or DDK. Our study revealed multi-layered phosphorylation-dependent regulation of the localisation of Mps3 on NE for meiotic chromosome motion and NE remodelling.

Biogenesis, inheritance, and 3D ultrastructure of the microsporidian mitosome

“…Interestingly, MPS3 signals did not overlap completely with TUB4 and were more closely related to the nuclear DAPI signal ( Figs 2B and S3 ). Some MPS3 signals were elongated and separated from the TUB4 signal, consistent with diverse and previously described nuclear functions in yeast ( Prasada Rao et al, 2021 ; Fig 2B ).…”

Meiotic DNA double‐strand break‐independent role of protein phosphatase 4 in Hop1 assembly to promote meiotic chromosome axis formation in budding yeast

“…There are two predicted CDK phosphorylation motifs (S/T‐P) in Hop1: S494 and S531 (Zhu et al, 2010). The presence of sequential phosphorylation by CDK followed by DDK in the sequence of serine/threonine residues in addition to the CDK phosphorylation motif has been described for related target proteins such as Mer2 (Wan et al, 2006) and Mps3 (Prasada Rao et al, 2021), and the S494 of Hop1 overlaps this motif (T‐S‐ 494 S‐P). In addition to these, it remains possible that slight Tel1/Mec1 kinase activity during the premeiotic S‐phase is sufficient for the regulation of Hop1 loading in the pCLB2‐MEC1 allele.…”

Rapid meiotic prophase chromosome movements inArabidopsis thalianaare linked to essential reorganization at the nuclear envelope

“…Mechanisms that control the redistribution and accumulation of the meiotic SUN domain-containing proteins at the interface between chromosomes and NE during meiotic prophase only started to be understood. However, they seem to involve direct phosphorylation of SUN proteins 93–95 . This accumulation of LINC complexes at the extremities of the telomeres is likely to correspond to the “attachment plates”, an electron-dense structure described in mammals that connects the synaptonemal complex with the inner nuclear membrane 96,97 .…”