Fig. 1
From: Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction
The cytoskeletal interactions of the LINC Complex and Nesprin at the Nuclear Envelope. Giant Nesprin-1/2 localizes to the nuclear membrane and interacts with SUN-1/2, facilitating the formation of the LINC complex, which physically connects the cytoskeleton and the nucleus. The KASH domain of Nesprins, located at the outer nuclear membrane (ONM), interacts with the SUN domain situated in the perinuclear space (PNS), found between the ONM and inner nuclear membrane (INM). Each Nesprin isoform (Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, and KASH5) exhibits specific positioning, forming distinct interactions with SUN proteins and displaying unique affinities for various cytoskeletal components. Nesprin-1/2 interact with SUN proteins in the perinuclear space and associate with actin filaments, playing a critical role in linking the nucleus to the actin cytoskeleton. Nesprin-3, located at the ONM, interacts with SUN proteins and exhibits a specific association with intermediate filaments, facilitating the connection between the nucleus and intermediate filament networks. Nesprin-4 interacts with SUN proteins in the perinuclear space and demonstrates an affinity for microtubules, contributing to tethering the nucleus to the microtubule cytoskeleton. KASH5, exclusive to meiotic cells, acts as an activator adapter for motor proteins, revealing the hierarchical assembly of the KASH5-motor protein-dynein complex. Nesprin-4 and KASH5 interact with microtubule motor proteins, including kinesin-1 or dynein/dynactin complexes