Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin.
Despite their importance in cell biology, the mechanisms that maintain the nucleus in its proper position in the cell are not well understood. This is primarily the result of an incomplete knowledge of the proteins in the outer nuclear membrane (ONM) that are able to associate with the different cytoskeletal systems. Two related ONM proteins, nuclear envelope spectrin repeat (nesprin)-1 and -2, are known to make direct connections with the actin cytoskeleton through their NH2-terminal actin-binding domain (ABD). We have now isolated a third member of the nesprin family that lacks an ABD and instead binds to the plakin family member plectin, which can associate with the intermediate filament (IF) system. Overexpression of nesprin-3 results in a dramatic recruitment of plectin to the nuclear perimeter, which is where these two molecules are colocalized with both keratin-6 and -14. Importantly, plectin binds to the integrin alpha6beta4 at the cell surface and to nesprin-3 at the ONM in keratinocytes, suggesting that there is a continuous connection between the nucleus and the extracellular matrix through the IF cytoskeleton.
Wilhelmsen
Kevin
K
Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Litjens
Sandy H M
SH
Kuikman
Ingrid
I
Tshimbalanga
Ntambua
N
Janssen
Hans
H
van den Bout
Iman
I
Raymond
Karine
K
Sonnenberg
Arnoud
A
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D039161:Integrin alpha6beta4 / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D051190:Plectin / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D039161:Integrin alpha6beta4; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051190:Plectin; C507800:nesprin-3 protein, mouse; D007633:Keratins