Expression of individual mammalian Sun1 isoforms depends on the cell type

Abstract

Mammalian Sun1 belongs to an evolutionarily conserved family of inner nuclear membrane proteins, which are known as SUN domain proteins. SUN domain proteins interact with KASH domain partners to form bridging complexes, so-called LINC complexes, that physically connect the nuclear interior to the cytoskeleton. LINC complexes are critical for nuclear integrity and play fundamental roles in nuclear positioning, shaping and movement. The mammalian genome codes for at least five different SUN domain proteins used for the formation of a number of different LINC complexes. Recently, we reported on the identification of several Sun1 isoforms, which tremendously enlarges the alternatives to form functional LINC complexes. We now confirmed that Sun1 actually exists in at least seven distinct splice variants. Besides that, we observed that expression of individual Sun1 isoforms remarkably depends on the cell type, suggesting a cell type-specific adaption of Sun1 dependent LINC complexes to specific cellular and physiological requirements.

SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration

“…The amplicons were analyzed in 6% TBE polyacrylamide gels. Similar to mouse SUN1, 34 the shortest SUN1 variant, SUN1_702, could be detected exclusively in testis but not in any somatic tissues tested.…”

“…35 This variant, which is referred to as SUN1_916 in this report, corresponds to the largest mouse SUN1 variant, composed of 913 aa, that predominates in most mouse tissues. 34 In addition to well-known variants, we identified a novel SUN1 splice variant; SUN1_888, which encodes 888 aa (AB648918, Fig. 1A and B, and details in the Materials and Methods).…”

“…[30][31][32] Third, in addition to variations of oligomer formation and post-translational modification, alternative splicing generates a huge number of SUN and nesprin variants. 4,33,34 The human SUN1 gene is located at chromosome position 7p22.3 and has 22 exons that encode up to 916 amino acids residues. Thus splice variants of SUN and nesprin may be responsible for diverse functions via different interacting components.…”

SUN4 is essential for nuclear remodeling during mammalian spermiogenesis

“…At least two additional SUN1 isoforms are also expressed in testis. One of these is missing exon 7 (SUN17), while the other lacks exons 7 and 9 (SUN17,9, Figure S2A) (Göb et al, 2011). We raised an antibody against these two isoform by immunizing rabbits with a peptide spanning the exon 6-8 junction ( Figure S2A).…”

“…This view is reinforced by observations on the disposition of certain SUN1 splice isoforms that are also expressed during spermiogenesis. One of these, SUN1 lacks exons 7-10 ( Figure S2A) (Göb et al, 2011;Göb et al, 2010), which encode sequences within the SUN1 nucleoplasmic domain immediately adjacent to the transmembrane region. While exogenous SUN1 localizes largely to the NE in HeLa cells (see Figure 4C in the paper by (Liu et al, 2007)), in spermatids it is suggested to reside in the acrosomal membrane where it may act as a tether for Nesprin 3.…”