De insight in to the intermediate nuclear migration defect. Some nuclei inside the unc-84(P91S) mutant background migrated typically, whereas other individuals failed. With the failed nuclei, many initiated migration normally before stopping aspect way via, whereas other folks 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 through the nuclear envelope to beta-lactamase-IN-1 custom synthesis transfer forces generated within the cytoplasm across the nuclear envelope. UNC-83 around the cytoplasmic surface of the 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 between KASH and SUN domains (Sosa et al., 2012; Tapley and Starr, 2013). Lastly, UNC-84 spans the inner nuclear membrane (Tapley et al., 2011) and interacts with lamin (Figure two) to complete the connection in between the cytoskeleton towards the nucleoskeleton (Figure 8). Even so, the amount of force that may be transferred across the nuclear envelope by the KASHSUN molecular bolt without the need of stabilization by an interaction using the nucleoskeleton is restricted. It is useful to believe of this complex as analogous to a nut and bolt in drywall, where the interaction of UNC-84 with nucleoskeletal components dissipates forces across a larger region along the inside in the wall, lowering the likelihood of failures beneath tension. In our model, LMN-1 functions as a important component in the molecular nut and washer to dissipate the forces transmitted across the KASHSUN bolt to structural components inside the nucleus. The LMN-1 nut and washer are only as strong because the interaction with all the UNC-84 nucleoplasmic domain on 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 devoid of lamin serving as a nut and washer. Having said that, at some essential point the forces are too strong, and the KASH SUN bolt is catastrophically detached, leading to a failure in nuclear migration. The stability from the bolt will depend on many elements. It truly is therefore difficult 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 8: Nut-and-bolt model for nuclear migration. Cartoon from the KASHSUN nuclear envelope bridge during nuclear migration. UNC-83 is shown in blue, with all the KASH peptide in teal. UNC-84 is shown with the SUN domain in red, the domain spanning the perinuclear space in black, along with 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 having a single microtubule in orange. Question marks symbolize open questions concerning protein interactions.nuclear envelope to chromatin (Simon and Wilson, 2011). It’s therefore unlikely that lamin B may be the only element from the molecular nut and washer that dissipates forces throughout the nucleoskeleton through nuclear migration. Clear candidates to participate with lamins in the course of nuclear migration include things like the LEM proteins, Baf, and Ima1NET5Samp1. In C. elegans, mutations in baf-1 or double m.