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.

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Figure 4. The LINC complex as a nuclear membrane spacer. SUN and KASH domain proteins (blue and yellow) are TM proteins of the INM and the ONM, respectively. SUN-KASH complexes may serve as nuclear membrane spacers and determine the regular shape of the NE. Observed INM-ONM distances in mammalian cells fit well the luminal sizes of both SUN1 and SUN2 given that their coiled coil regions form continuous and extended structures. Analogously, other LINC complexes might determine the spacing of the nuclear membranes in different cell types or species.
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Figure 4: Figure 4. The LINC complex as a nuclear membrane spacer. SUN and KASH domain proteins (blue and yellow) are TM proteins of the INM and the ONM, respectively. SUN-KASH complexes may serve as nuclear membrane spacers and determine the regular shape of the NE. Observed INM-ONM distances in mammalian cells fit well the luminal sizes of both SUN1 and SUN2 given that their coiled coil regions form continuous and extended structures. Analogously, other LINC complexes might determine the spacing of the nuclear membranes in different cell types or species.

Mentions: LINC complexes may in fact serve as the molecular rulers, which set the distance between the INM and the ONM.8 When the luminal region of SUN2 preceding the SUN domain is extrapolated as a continuous and extended, trimeric coiled coil, it reaches a length of ~45 nm.27 Together with the globular SUN domain assembly, the entire luminal portion of SUN2 would thus span a distance of ~48 nm, fitting strikingly well the observed spacing of the nuclear membranes in mammalian cells (Fig. 4).28 Importantly, domain organization and size of the luminal parts are conserved between SUN1 and SUN2 (Fig. 1). Although it cannot be excluded that they simply represent adaptions to a given membrane distance, the existing experimental evidence clearly points toward an active and collaborative role of LINC complexes in shaping the mammalian NE.8,10


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 4. The LINC complex as a nuclear membrane spacer. SUN and KASH domain proteins (blue and yellow) are TM proteins of the INM and the ONM, respectively. SUN-KASH complexes may serve as nuclear membrane spacers and determine the regular shape of the NE. Observed INM-ONM distances in mammalian cells fit well the luminal sizes of both SUN1 and SUN2 given that their coiled coil regions form continuous and extended structures. Analogously, other LINC complexes might determine the spacing of the nuclear membranes in different cell types or species.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Figure 4. The LINC complex as a nuclear membrane spacer. SUN and KASH domain proteins (blue and yellow) are TM proteins of the INM and the ONM, respectively. SUN-KASH complexes may serve as nuclear membrane spacers and determine the regular shape of the NE. Observed INM-ONM distances in mammalian cells fit well the luminal sizes of both SUN1 and SUN2 given that their coiled coil regions form continuous and extended structures. Analogously, other LINC complexes might determine the spacing of the nuclear membranes in different cell types or species.
Mentions: LINC complexes may in fact serve as the molecular rulers, which set the distance between the INM and the ONM.8 When the luminal region of SUN2 preceding the SUN domain is extrapolated as a continuous and extended, trimeric coiled coil, it reaches a length of ~45 nm.27 Together with the globular SUN domain assembly, the entire luminal portion of SUN2 would thus span a distance of ~48 nm, fitting strikingly well the observed spacing of the nuclear membranes in mammalian cells (Fig. 4).28 Importantly, domain organization and size of the luminal parts are conserved between SUN1 and SUN2 (Fig. 1). Although it cannot be excluded that they simply represent adaptions to a given membrane distance, the existing experimental evidence clearly points toward an active and collaborative role of LINC complexes in shaping the mammalian NE.8,10

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