Nesprin-3 links the nucleus to the intermediate filaments through the binding to the cytoskeletal linker protein plectin []. It is a component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, which plays critical roles in nuclear positioning, cell polarisation and cellular stiffness []. Nesprin-3 can also connect the nucleus to microtubules by its interactions with BPAG1 (bullous pemphigoid antigen 1) and MACF (microtubule-actin cross-linking factor) []. Nesprin-3 contains a conserved Klarsicht/ANC-1/Syne homology (KASH) domain at its C terminus that can associate with Sad1p/UNC-84 (SUN)-domain proteins of the inner nuclear membrane within the periplasmic space of the nuclear envelope (NE) []. It also has a plectin-binding motif that permits interactions with cytoplasmic intermediate filaments [].
