Limits...
LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function.

Rothballer A, Schwartz TU, Kutay U - Nucleus (2013)

Bottom Line: The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM).Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling.They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.

ABSTRACT
Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM). In the lumen of the NE, the SUN and KASH domains engage in an intimate assembly to jointly form a NE bridge. Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling. They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

Show MeSH

Related in: MedlinePlus

Figure 1. Typical SUN domain proteins. Typical SUN domain proteins contain one TM region (red). Their N-terminal portions localize in the nucleo/cytoplasm, while their C-terminal portions, consisting of a coiled coil region (blue) and the conserved SUN domain (orange), are exposed to the lumen of the NE/ER. TM regions, coiled coils and SUN domains are indicated based on bioinformatic predictions (TMHMM2, parcoil2, prosite), literature and visual comparison of homologs. Note that additional hydrophobic stretches or potential TM regions are present in most SUN domain proteins, but have been omitted from the scheme for clarity. Further, although only short coiled coil elements are predicted (solid blue), it is conceivable that the entire luminal region preceding the SUN domain forms one continuous coiled coil (blue shadow, length indicated).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3585024&req=5

Figure 1: Figure 1. Typical SUN domain proteins. Typical SUN domain proteins contain one TM region (red). Their N-terminal portions localize in the nucleo/cytoplasm, while their C-terminal portions, consisting of a coiled coil region (blue) and the conserved SUN domain (orange), are exposed to the lumen of the NE/ER. TM regions, coiled coils and SUN domains are indicated based on bioinformatic predictions (TMHMM2, parcoil2, prosite), literature and visual comparison of homologs. Note that additional hydrophobic stretches or potential TM regions are present in most SUN domain proteins, but have been omitted from the scheme for clarity. Further, although only short coiled coil elements are predicted (solid blue), it is conceivable that the entire luminal region preceding the SUN domain forms one continuous coiled coil (blue shadow, length indicated).

Mentions: It has long been suggested that SUN domain proteins form oligomers. This idea was based on the prediction of coiled coil elements preceding the C-terminal SUN domain in the luminal part of all typical SUN homologs (Figs. 1 and 2) ), as well as on the oligomerization of the coiled coil region of human SUN1 in vitro. An organization of SUN domain proteins as homo- or heterodimers had been widely assumed.5-7


LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function.

Rothballer A, Schwartz TU, Kutay U - Nucleus (2013)

Figure 1. Typical SUN domain proteins. Typical SUN domain proteins contain one TM region (red). Their N-terminal portions localize in the nucleo/cytoplasm, while their C-terminal portions, consisting of a coiled coil region (blue) and the conserved SUN domain (orange), are exposed to the lumen of the NE/ER. TM regions, coiled coils and SUN domains are indicated based on bioinformatic predictions (TMHMM2, parcoil2, prosite), literature and visual comparison of homologs. Note that additional hydrophobic stretches or potential TM regions are present in most SUN domain proteins, but have been omitted from the scheme for clarity. Further, although only short coiled coil elements are predicted (solid blue), it is conceivable that the entire luminal region preceding the SUN domain forms one continuous coiled coil (blue shadow, length indicated).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585024&req=5

Figure 1: Figure 1. Typical SUN domain proteins. Typical SUN domain proteins contain one TM region (red). Their N-terminal portions localize in the nucleo/cytoplasm, while their C-terminal portions, consisting of a coiled coil region (blue) and the conserved SUN domain (orange), are exposed to the lumen of the NE/ER. TM regions, coiled coils and SUN domains are indicated based on bioinformatic predictions (TMHMM2, parcoil2, prosite), literature and visual comparison of homologs. Note that additional hydrophobic stretches or potential TM regions are present in most SUN domain proteins, but have been omitted from the scheme for clarity. Further, although only short coiled coil elements are predicted (solid blue), it is conceivable that the entire luminal region preceding the SUN domain forms one continuous coiled coil (blue shadow, length indicated).
Mentions: It has long been suggested that SUN domain proteins form oligomers. This idea was based on the prediction of coiled coil elements preceding the C-terminal SUN domain in the luminal part of all typical SUN homologs (Figs. 1 and 2) ), as well as on the oligomerization of the coiled coil region of human SUN1 in vitro. An organization of SUN domain proteins as homo- or heterodimers had been widely assumed.5-7

Bottom Line: The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM).Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling.They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.

ABSTRACT
Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the double membrane of the nuclear envelope (NE) and physically connect nuclear structures to cytoskeletal elements. LINC complexes are envisioned as force transducers in the NE, which facilitate processes like nuclear anchorage and migration, or chromosome movements. The complexes are built from members of two evolutionary conserved families of transmembrane (TM) proteins, the SUN (Sad1/UNC-84) domain proteins in the inner nuclear membrane (INM) and the KASH (Klarsicht/ANC-1/SYNE homology) domain proteins in the outer nuclear membrane (ONM). In the lumen of the NE, the SUN and KASH domains engage in an intimate assembly to jointly form a NE bridge. Detailed insights into the molecular architecture and atomic structure of LINC complexes have recently revealed the molecular basis of nucleo-cytoskeletal coupling. They bear important implications for LINC complex function and suggest new potential and as yet unexplored roles, which the complexes may play in the cell.

Show MeSH
Related in: MedlinePlus