Molecular mechanisms of centrosome and cytoskeleton anchorage at the nuclear envelope.
Cell Mol Life Sci
; 68(9): 1593-610, 2011 May.
Article
in En
| MEDLINE
| ID: mdl-20922455
ABSTRACT
Cell polarization is a fundamental process underpinning organismal development, and tissue homeostasis, which requires an orchestrated interplay of nuclear, cytoskeletal, and centrosomal structures. The underlying molecular mechanisms, however, still remain elusive. Here we report that kinesin-1/nesprin-2/SUN-domain macromolecular assemblies, spanning the entire nuclear envelope (NE), function in cell polarization by anchoring cytoskeletal structures to the nuclear lamina. Nesprin-2 forms complexes with the kinesin-1 motor protein apparatus by associating with and recruiting kinesin light chain 1 (KLC1) to the outer nuclear membrane. Similar to nesprin-2, KLC1 requires lamin A/C for proper NE localization. The depletion of nesprin-2 or KLC1, or the uncoupling of nesprin-2/SUN-domain protein associations impairs cell polarization during wounding and dislodges the centrosome from the NE. In addition nesprin-2 loss has profound effects on KLC1 levels, the cytoskeleton, and Golgi apparatus organization. Collectively these data show that NE-associated proteins are pivotal determinants of cell architecture and polarization.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytoskeleton
/
Centrosome
/
Cytoskeletal Proteins
/
Nuclear Envelope
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Mol Life Sci
Journal subject:
BIOLOGIA MOLECULAR
Year:
2011
Type:
Article
Affiliation country:
United kingdom