SUN4 is a spermatid type II inner nuclear membrane protein that forms heteromeric assemblies with SUN3 and interacts with lamin B3

Abstract

SUN domain proteins are conserved proteins of the nuclear envelope and key components of the LINC complexes (linkers of the nucleoskeleton and the cytoskeleton). Previous studies have demonstrated that the testis-specific SUN domain protein SUN4 is a vital player in the directed shaping of the spermatid nucleus. However, its molecular properties relating to this crucial function have remained largely unknown and controversial data for the organization and orientation of SUN4 within the spermatid nuclear envelope have been presented so far. Here we have re-evaluated this issue in detail and show robust evidence that SUN4 is integral to the inner nuclear membrane, sharing a classical SUN domain protein topology. The C-terminal SUN domain of SUN4 localizes to the perinuclear space, while the N-terminus is directed to the nucleoplasm, interacting with the spermiogenesis-specific lamin B3. We found that SUN4 forms heteromeric assemblies with SUN3 in vivo and regulates SUN3 expression. Together, our results contribute to a better understanding of the specific function of SUN4 at the spermatid nucleo-cytoplasmic junction and the process of sperm-head formation.

Protamine 2 Deficiency Results In Septin 12 Abnormalities

“…As described previously, Septin 12 can form a complex with Lamin B1 and SUN4 (a sperm-specific component of LINC complex) and is important for its correct positioning (Lin et al, 2009, Yeh et al, 2015, Yeh et al, 2019). Moreover, (Thoma et al, 2023) it has recently been shown that Lamin B3 interacts with SUN4 in vivo, but its localization is independent of SUN4, as shown on the SUN4 -/- mouse model. Based on our analysis, the amount of Lamin B2 and Lamin B3 in testicular cells of Prm2 -/- remains unchanged compared to WT.…”

Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro

“…SUN-domain proteins are evolutionarily conserved INM proteins. The human genome contains five SUN-domain genes; the ubiquitously expressed SUN1 and SUN2 , as well as SUN3 , SUN4 ( SPAG4 ), and SUN5 ( SPAG4L ), which exhibit a testis-specific expression pattern [ 2 , 14 , 15 , 16 , 17 , 18 , 19 ]. The hallmark of the protein family is the conserved C-terminal SUN-domain, which is preceded by a less-conserved coiled-coil segment, residing in the NE lumen.…”