page 799), by a relative of the nesprin actin-binding proteins.
Nesprin-1 and -2 connect the outer nuclear membrane to the actin cytoskeleton. Now, a third nesprin is identified that lacks actin-binding abilities but instead links to IFs. This linkage requires plectin, a keratin-binding protein, as a go-between. The authors show that nesprin-3 recruits plectin to the nuclear perimeter, where both proteins are colocalized with keratins, a type of IF.
Plectin, in addition to its nuclear localization, has also been found at hemidesmosomes, where it links IFs to a matrix-bound integrin. The two linkages imply a continuous IF network from the matrix to the nucleus. Nesprins interact with inner nuclear membrane proteins that are associated with lamins, which in turn influence chromatin and transcription factors. So, tug on a cell, and it is even possible that this long linkage might bring about transcriptional changes with far more speed than could any signaling pathway.
Nuclear links to the cytoskeleton are more traditionally thought of as essential for nuclear positioning. Proper nuclear alignment might be especially important in multi-nucleated cells, such as skeletal muscle fibers. The authors are knocking down nesprin-3 levels in muscle satellite cells to test this possibility.