Fig. 5.

The lamin-binding domain of SUN2 contains mechano-sensitive phosphorylation sites. a Schematic of SUN2 protein trimer spanning the NE and linking between the nuclear lamina and nesprins⁷¹. MS detected four mechano-responsive phosphorylation sites within the lamin-binding domain of SUN2. ONM = outer nuclear membrane; INM = inner nuclear membrane. b Amino acid sequence of SUN2 protein. Red indicates regions of the sequence detected by MS, showing coverage of domains across the length of the protein; phosphosites are also indicated. Domains are indicated according to the scheme shown in figure part (a). c Quantification of phosphorylation at sites in SUN2 (pThr9, pSer12, pSer21, pSer38) immediately, and 24 h following, CTS (1 h at 5 Hz, 2.6–6.2% strain; n = 3 donors). pS12, pS21 and pS38 showed an immediate response to strain (p = 0.007, <0.0001, and <0.0001, respectively); changes to pT9, pS12, and pS21 suggested more persistent remodeling (p = 0.003, <0.0001, and <0.0001, respectively). Data displayed as mean and s.e.m.; p-values were calculated using empirical Bayes-modified t-tests with Benjamini–Hochberg correction. d Summary of evidence that suggests a sequential mechanism for nuclear decoupling, and subsequent recovery, following high-intensity CTS