Sep 25, 2018

Conserved SUN-KASH Interfaces Mediate LINC Complex-Dependent Nuclear Movement and Positioning

Current Biology : CB
Natalie E CainDaniel A Starr

Abstract

Many nuclear positioning events involve linker of nucleoskeleton and cytoskeleton (LINC) complexes, which transmit forces generated by the cytoskeleton across the nuclear envelope. LINC complexes are formed by trans-luminal interactions between inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins, but how these interactions are regulated is poorly understood. We combine in vivo C. elegans genetics, in vitro wounded fibroblast polarization, and in silico molecular dynamics simulations to elucidate mechanisms of LINC complexes. The extension of the KASH domain by a single alanine residue or the mutation of the conserved tyrosine at -7 completely blocked the nuclear migration function of C. elegans UNC-83. Analogous mutations at -7 of mouse nesprin-2 disrupted rearward nuclear movements in NIH 3T3 cells, but did not disrupt ANC-1 in nuclear anchorage. Furthermore, conserved cysteines predicted to form a disulfide bond between SUN and KASH proteins are important for the function of certain LINC complexes, and might promote a developmental switch between nuclear migration and nuclear anchorage. Mutations of conserved cysteines in SUN or KASH disrupted ANC-1-dependent nuclear anchorage in C. elegans and Nespri...Continue Reading

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Mentioned in this Paper

Calcinus elegans
Inner Nuclear Membrane
Cyartonema elegans
Molecular Dynamics
In Vivo
Coleonyx elegans
Cestrum elegans
Clarkia unguiculata
Specimen Type - Fibroblasts
Clathrulina elegans

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