LARRY R GERACE

..Understanding the structure of the lamina from the atomic to supramolecular levels will be essential for achieving this goal...

..Considered together, these data indicate that lamins play a major role in organizing other proteins in the nuclear envelope and in determining nuclear shape...

..These results indicate that nucleoporins themselves, as well as the nucleocytoplasmic compartmentalization of the Ran system, are likely to play an important role in conferring directionality to nuclear protein import...

..We also investigated the conditions required for nuclear import of Tpr using an in vitro assay...

..Our goal was to identify new nuclear envelope and lamina components whose expression is coordinated with muscle differentiation...

..Comparative proteomics of organellar subfractions can mitigate these problems, as demonstrated by a recent study involving the nuclear envelope...

....

..We have analysed the expression of these proteins using transcriptome databases, providing direction for future functional analysis of these novel proteins...

..Nuclear injection of anti-Tpr antibodies in interphase cells similarly yielded inhibition of protein export but not import. These results indicate that Tpr is a nucleoporin of the nuclear basket with a role in nuclear protein export...

..These data support a mechanism of receptor-mediated nuclear import of PLSCR1 and suggest a potential nuclear function for this plasma membrane protein...

....

..Furthermore, 23 of these mapped within chromosome regions linked to a variety of dystrophies...

..Our work supports the hypothesis that deregulation of cell signaling contributes to NE-linked disorders and suggests that mutations in NET25 and MAN1 may cause muscle diseases...

..The localization of NET37 at the nuclear envelope raises the possibility that it may coordinate myogenic events between the nuclear interior and the endoplasmic reticulum lumen via transmembrane communication...

..Our results indicate that NET39 is part of the regulatory machinery for myogenesis and raise the possibility that it may be important for muscle homeostasis...

..We suggest that RanGTP functions in these pathways to promote the transport of large cargo by enhancing the ability of import complexes to traverse diffusionally restricted areas of the NPC...

..We propose that this region contains a prototypical nuclear import receptor domain, which could have evolved into the modern importin beta superfamily...

..These studies identify a previously undescribed mechanism by which neutralizing antibodies block virus infection, a situation that may be relevant for other nonenveloped viruses that use microtubule-dependent transport during cell entry...

..The removal of these C-terminal transport signals appears to trigger a functional transition in protein VI, from a role in supporting hexon nuclear import to a structural role in virus assembly...

..593 of this issue) found that the sizes of individual nuclei are controlled by the relative amount of cytoplasm surrounding each nucleus. These results highlight a role of the cytoplasm in nuclear size control...

..The prevalence of L18T in infected individuals suggests a positive selection mechanism for L18T modulation of Rev activity that may delay the onset of AIDS...

....

..Thus, importin beta possesses two nucleoporin binding sites, both of which are important for its nuclear import function...

..abstract_text> ..

..Since nuclear transport is integrally involved in gene expression, this project has direct relevance to a number of human health issues including cancer, viral pathogenesis, immunity and aging. ..

....

....

..Finally, it could provide the basis for developing efficient means for nonviral gene transfer, which would be useful for gene therapy and functional studies of cells. ..

..Thus, understanding basic nuclear transport mechanisms can provide a framework for developing new therapeutic approaches relevant to viral pathogenesis, cancer and immunity and other processes. ..

..Finally, it could provide the basis for developing efficient means for nonviral gene transfer, which would be useful for gene therapy and functional studies of cells. ..

..Together this set of approaches is expected to significantly advance current understanding of the nuclear lamina, and contribute to knowledge of how aberrations in nuclear organization can promote human disease states such as cancer. ..

..Collectively, these studies will provide a paradigm for approaching study of RNA export from the nucleus, which probably shares many features with protein import...

..Together this work should provide important new insight on major karyoskeletal functions of the lamina...

....