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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 2. Atypical SUN domain proteins. Besides the typical SUN domain proteins, an unusual second subfamily exists. This subfamily is also highly conserved throughout evolution and includes, for instance, human SUCO/C1ORF9, Saccharomyces cerevisiae Slp1 (SUN-like protein 1) and several plant homologs like Zea mays SUN4. Interestingly, ZmSUN4 has recently been shown to concentrate in the nuclear periphery in maize.60 The domain structure of this type of SUN domain proteins is strikingly different to the conventional one. The SUN domain is located in the middle of the protein instead of at the C terminus and is followed—and not as usual preceded—by a putative coiled coil region. Further, the proteins are potentially membrane-anchored at both their N and C termini and might thus form NE bridges independently of binding partners. Presently, it is unclear if these atypical SUN domain proteins interact with KASH-like peptides and whether they function in force transduction, NE spacing or membrane fusion. Most likely, however, their distinct domain structure, i.e., the inverse order of SUN domain, coiled coils and membrane anchor, might reflect a unique role of these proteins in the NE. TM regions, coiled coils and SUN domains were predicted as in Figure 1. A novel type of SUN domain proteins in the nuclear envelope.
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Figure 2: Figure 2. Atypical SUN domain proteins. Besides the typical SUN domain proteins, an unusual second subfamily exists. This subfamily is also highly conserved throughout evolution and includes, for instance, human SUCO/C1ORF9, Saccharomyces cerevisiae Slp1 (SUN-like protein 1) and several plant homologs like Zea mays SUN4. Interestingly, ZmSUN4 has recently been shown to concentrate in the nuclear periphery in maize.60 The domain structure of this type of SUN domain proteins is strikingly different to the conventional one. The SUN domain is located in the middle of the protein instead of at the C terminus and is followed—and not as usual preceded—by a putative coiled coil region. Further, the proteins are potentially membrane-anchored at both their N and C termini and might thus form NE bridges independently of binding partners. Presently, it is unclear if these atypical SUN domain proteins interact with KASH-like peptides and whether they function in force transduction, NE spacing or membrane fusion. Most likely, however, their distinct domain structure, i.e., the inverse order of SUN domain, coiled coils and membrane anchor, might reflect a unique role of these proteins in the NE. TM regions, coiled coils and SUN domains were predicted as in Figure 1. A novel type of SUN domain proteins in the nuclear envelope.

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 2. Atypical SUN domain proteins. Besides the typical SUN domain proteins, an unusual second subfamily exists. This subfamily is also highly conserved throughout evolution and includes, for instance, human SUCO/C1ORF9, Saccharomyces cerevisiae Slp1 (SUN-like protein 1) and several plant homologs like Zea mays SUN4. Interestingly, ZmSUN4 has recently been shown to concentrate in the nuclear periphery in maize.60 The domain structure of this type of SUN domain proteins is strikingly different to the conventional one. The SUN domain is located in the middle of the protein instead of at the C terminus and is followed—and not as usual preceded—by a putative coiled coil region. Further, the proteins are potentially membrane-anchored at both their N and C termini and might thus form NE bridges independently of binding partners. Presently, it is unclear if these atypical SUN domain proteins interact with KASH-like peptides and whether they function in force transduction, NE spacing or membrane fusion. Most likely, however, their distinct domain structure, i.e., the inverse order of SUN domain, coiled coils and membrane anchor, might reflect a unique role of these proteins in the NE. TM regions, coiled coils and SUN domains were predicted as in Figure 1. A novel type of SUN domain proteins in the nuclear envelope.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Figure 2. Atypical SUN domain proteins. Besides the typical SUN domain proteins, an unusual second subfamily exists. This subfamily is also highly conserved throughout evolution and includes, for instance, human SUCO/C1ORF9, Saccharomyces cerevisiae Slp1 (SUN-like protein 1) and several plant homologs like Zea mays SUN4. Interestingly, ZmSUN4 has recently been shown to concentrate in the nuclear periphery in maize.60 The domain structure of this type of SUN domain proteins is strikingly different to the conventional one. The SUN domain is located in the middle of the protein instead of at the C terminus and is followed—and not as usual preceded—by a putative coiled coil region. Further, the proteins are potentially membrane-anchored at both their N and C termini and might thus form NE bridges independently of binding partners. Presently, it is unclear if these atypical SUN domain proteins interact with KASH-like peptides and whether they function in force transduction, NE spacing or membrane fusion. Most likely, however, their distinct domain structure, i.e., the inverse order of SUN domain, coiled coils and membrane anchor, might reflect a unique role of these proteins in the NE. TM regions, coiled coils and SUN domains were predicted as in Figure 1. A novel type of SUN domain proteins in the nuclear envelope.
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