UNC-83 is a mostly novel protein required for nuclear migration events in a variety of C. elegans tissues. The role of UNC-83 in nuclear migration, its structural significance, and its direct protein partners are not known. It was previously shown that UNC-83 is recruited to the nuclear envelope by UNC-84, a likely inner nuclear membrane protein with a conserved C-terminal SUN domain 1-3 . Specifically, point mutations in the conserved SUN domain of UNC-84 disrupted UNC-83 localization. ANC-1, a protein required to tether nuclei to the actin cytoskeleton and anchor nuclei in place, is also recruited to the nuclear envelope by the SUN domain of UNC-84. The C-terminal KASH ( K larsicht, A NC-1, S yne-1 h omology) domain of ANC-1 is required for nuclear envelope localization 4 . Upon closer examination of the C-terminus of UNC-83, we identified a possible KASH domain. Eight of the last seventeen residues of UNC-83 are identical to other KASH domains. A predicted membrane-spanning domain immediately precedes these residues, which is the same case in all the other KASH domains. We therefore hypothesized that UNC-83 contains a C-terminal KASH domain that is responsible for the localization of UNC-83 to the nuclear envelope through an interaction with the SUN domain of UNC-84 in the intermembrane space of the nuclear envelope. We show here that mutations in the C-terminus of UNC-83 disrupt nuclear migration, supporting our proposed model. To test the dependence of the KASH domain for the function of UNC-83, we created multiple point mutations and small deletions in the minimal rescuing fragment of unc-83 . These constructs include deletions of C-terminal amino acids and mutations of highly conserved amino acids in the KASH domain. Transgenic lines were created in an unc-83(e1408) background for each mutant construct. The transgenic animals were screened for rescue of hyp 7 cell nuclear migration defects, and localization of UNC-83 to the nuclear envelope. Deletion of the C-terminal 17 residues of UNC-83 blocks both the function and localization of UNC-83 at the nuclear envelope. Thus, the KASH domain of UNC-83 is necessary for nuclear envelope localization. Furthermore, a number of point mutations in the KASH domain of UNC-83 also disrupt UNC-83 function. We are also in the process of testing the sufficiency of the KASH domain for nuclear envelope localization. We are also testing whether the KASH domain of UNC-83 can be replaced by other KASH domains. Preliminary results suggest that a human KASH domain is not sufficient to localize UNC-83 to the nuclear envelope. Finally, we are testing whether the KASH domain of UNC-83 directly interacts with the SUN domain of UNC-84. 1. Malone, C. J. et al. Devel. 126, 3171-81 (1999). 2. Starr, D. A. et al. Development 128, 5039-50 (2001). 3. Lee, K. K. et al. Mol. Biol. of the Cell 13, 892-901 (2002). 4. Starr, D. A. & Han, M. Science 298, 406-409 (2002).