De insight in to the intermediate nuclear migration defect. Some nuclei within the unc-84(P91S) mutant background migrated normally, whereas other people failed. From the failed nuclei, lots of initiated migration generally just before stopping part way by means of, whereas other individuals failed to move at all. Of interest, we didn’t see slow-moving nuclei in unc-84(P91S) embryos; the nuclei that did move did so similarly to wild-type nuclei. Our proposed model is shown in Figure 8. Within this model, KASH SUN bridges serve as molecular bolts by way of the nuclear envelope to transfer forces generated within the cytoplasm across the nuclear envelope. UNC-83 on the cytoplasmic surface of your nuclear envelope interacts with microtubule motors kinesin-1 and dynein (Meyerzon et al., 2009a; Fridolfsson et al., 2010). The forces generated by the motors are transmitted across the outer nuclear membrane by UNCVolume 25 September PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21266802 15,83 and after that to the SUN protein UNC-84 by way of an interaction among KASH and SUN domains (Sosa et al., 2012; Tapley and Starr, 2013). Ultimately, UNC-84 spans the inner nuclear membrane (Tapley et al., 2011) and interacts with lamin (Figure two) to finish the connection between the cytoskeleton towards the nucleoskeleton (Figure eight). On the other hand, the amount of force that may be transferred across the nuclear envelope by the KASHSUN molecular bolt without having stabilization by an interaction together with the nucleoskeleton is limited. It’s useful to believe of this complicated as analogous to a 
nut and bolt in drywall, exactly where the interaction of UNC-84 with nucleoskeletal components dissipates forces across a larger area along the inside with the wall, lowering the likelihood of failures under tension. In our model, LMN-1 functions as a key element from the molecular nut and washer to dissipate the forces transmitted across the KASHSUN bolt to structural elements inside the nucleus. The LMN-1 nut and washer are only as robust as the interaction together with the UNC-84 nucleoplasmic D,L-3-Indolylglycine site domain of the bolt. If the UNC-84LMN-1 interaction fails, as in the UNC-84(P91S) mutant, the nucleus could continue to migrate for some time with out lamin serving as a nut and washer. Even so, at some essential point the forces are also powerful, along with the KASH SUN bolt is catastrophically detached, major to a failure in nuclear migration. The stability of the bolt depends on many things. It really is thus hard to predict when the KASHSUN bridge will fail, explaining why some UNC-84(P91S) nuclei fail at the initiation ofSUN amin interactions to move nucleiFIGURE eight: Nut-and-bolt model for nuclear migration. Cartoon of your KASHSUN nuclear envelope bridge throughout nuclear migration. UNC-83 is shown in blue, together with the KASH peptide in teal. UNC-84 is shown with the SUN domain in red, the domain spanning the perinuclear space in black, and also the nucleoplasmic domain in yellow. The green asterisks indicate the P91S mutation in UNC-84. LMN-1 is shown in dark blue and SAMP-1 in fuchsia. Microtubule motors are shown in black and white interacting with a single microtubule in orange. Query marks symbolize open questions relating to protein interactions.nuclear envelope to chromatin (Simon and Wilson, 2011). It truly is consequently unlikely that lamin B may be the only element of the molecular nut and washer that dissipates forces throughout the nucleoskeleton during nuclear migration. Apparent candidates to participate with lamins through nuclear migration contain the LEM proteins, Baf, and Ima1NET5Samp1. In C. elegans, mutations in baf-1 or double m.