nesprin4

Nesprin-4, also known as SYNE4, is a member of the Nesprin family of spectrin-repeat-containing proteins that form part of the linker of nucleoskeleton and cytoskeleton (LINC) complex. In humans, Nesprin-4 is encoded by the SYNE4 gene. Like other nesprins, it is a tail-anchored outer nuclear membrane (ONM) protein that contains a KASH (Klarsicht/ANC-1/Syne) domain at its C-terminus, which anchors it to SUN proteins in the inner nuclear membrane and thereby connects the cytoskeleton to the nuclear envelope.

Functionally, Nesprin-4 contributes to nuclear positioning and movement by linking cytoskeletal elements to the nucleus. It has been reported to recruit the microtubule-based motor kinesin-1 to the nuclear envelope, enabling microtubule-dependent nuclear transport and positioning, particularly in polarized or differentiated cells. Through interaction with SUN1/2, Nesprin-4 participates in the LINC complex that transmits mechanical forces between the cytoskeleton and the nucleus and helps maintain nuclear integrity during cellular deformation.

Expression and relevance of Nesprin-4 are detected across multiple tissues, and its role is understood within the broader context of LINC complex function. Disruption of LINC components can affect nuclear positioning, mechanotransduction, and cell polarity; while specific disease associations for SYNE4 mutations are less well defined than for some other nesprins, Nesprin-4 is considered a component of the nuclear envelope–cytoskeleton linkage relevant to development and disease in the broader Nesprin research field.

See also: LINC complex; SUN proteins; KASH-domain proteins; SYNE family.