SUN proteins and nuclear envelope spacing

Abstract

T he nuclear envelope consists of 2 membranes separated by 30-50 nm, but how the 2 membranes are evenly spaced has been an open question in the field. Nuclear envelope bridges composed of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins have been proposed to set and regulate nuclear envelope spacing. We tested this hypothesis directly by examining nuclear envelope spacing in Caenorhabditis elegans animals lacking UNC-84, the sole somatic SUN protein. SUN/ KASH bridges are not required to maintain even nuclear envelope spacing in most tissues. However, UNC-84 is required for even spacing in body wall muscle nuclei. Shortening UNC-84 by 300 amino acids did not narrow the nuclear envelope space. While SUN proteins may play a role in maintaining nuclear envelope spacing in cells experiencing forces, our data suggest they are dispensable in most cells.

Noncentrosomal microtubules in C. elegans epithelia

“…Interestingly, kinesin-1 provides the major force to drag the nucleus towards the plus-end of MTs, whereas dynein fine-tunes the process by imposing smaller amplitude movements in the opposite direction . The mechanical forces exerted by the cytoskeleton are probably transmitted to the nucleoskeleton through a specific interaction between the SUN protein UNC-84 and the nuclear lamin, (Bone et al, 2014;Cain and Starr, 2015). Importantly, the molecular mechanism controlling nuclear positioning are evolutionary conserved, since the human LINC complex can partially rescue the hyp7 defective nuclear migration of double unc-83; unc-84 mutants (Cain et al, 2014).…”

The LINC and NPC relationship – it's complicated!

“…However, there is currently no evidence that sperm cells or other cell types with shorter SUN proteins have reduced PNS spacing. Furthermore, shortening of the SUN protein UNC-84 in C. elegans does not result in any observable narrowing of the PNS and, interestingly, also did not disrupt nucleocytoskeletal coupling (Cain et al, 2014;Cain and Starr, 2015). The mechanisms by which shorter SUN proteins overcome the PNS gap to bind to KASH-domain proteins and mediate nucleocytoskeletal coupling remains unclear.…”

“…(B) Second model. LINC complexes adapt to the pre-determined thickness of the nuclear envelope by extending their luminal regions so they span the entire nuclear envelope thickness (Cain and Starr, 2015;Cain et al, 2014). (C) Increased nuclear envelope spacing is observed upon disruption of LINC complexes, while the nuclear envelope remains intact around NPCs (Crisp et al, 2006;Cain et al, 2014).…”

“…LINC complexes entirely determine the thickness of the nuclear envelope. Therefore, a locally reduced nuclear envelope thickness should be observed with shorter SUN proteins, such as testis-specific SUN3, SUN4 or SUN5 compared with that containing SUN1 and SUN2, although it might not be possible to resolve this using current microscopy techniques (Sosa et al, 2013;Cain and Starr, 2015;Cain et al, 2014). The integrity of the nuclear envelope is maintained despite the cytoskeletal forces (blue arrows) that act on LINC complexes.…”

“…Currently, two potential mechanisms have been proposed: (i) LINC complexes composed of shorter SUN proteins either locally pinch the nuclear envelope (Fig. 4A) or (ii) SUN proteins adapt to the existing PNS thickness by extending their luminal domains (Cain and Starr, 2015) (Fig. 4B).…”