The nuclear lamina and pore complex organization

Abstract

The nuclear envelope forms a distinct boundary between the nucleus and newlinecytoplasm in all eukaryotic cells. It has a complex organization consisting of the inner and newlineouter nuclear membranes, nuclear pore complexes and the nuclear lamina. The nuclear lamina newlineis a fibrous network of proteins that lines the inner nuclear membrane and performs essential newlinefunctions during envelope disassembly and assembly at mitosis. The lamina also provides newlineattachment sites for the interphase chromatin. The pore complexes provide channels for newlinemolecular exchange between the nucleus and cytoplasm. newlineNuclear import of proteins is a selective and energy-dependent process, requiring newlinethe presence of a nuclear localization signal (NLS) on the karyophilic protein. Transport newlineoccurs in at least two steps. The first step, binding to the pore, is due to specific recognition newlineof the transport signal and does not require A TP. The second step, translocation through the newlinepore, is ATP-dependent. newlineThe major structural proteins of the nuclear lamina are the nuclear lamins. The newlinevertebrate lamins can be grouped into A-type and B-type lamins. While B-type lamins are newlineconstitutively expressed, the expression of A-type lamins is regulated during development. newlineThe purpose of undertaking this work was firstly, to identify membrane-anchorage newlinesites of the nuclear lamina using chemical cross-linking agents. Secondly, the nuclear newlineenvelope-associated ATPase was studied in relation to the effect of NLS-receptor interaction newlineon its activity. Thirdly, the expression oflamins during rat liver development was determined newlineusing an antibody raised against bacterially-expressed laminA protein. Finally, the expression newlineof a specific class of pore complex proteins during development was studied, and the ability newlineVll newlineof antibodies to these proteins to block transport of nuclear proteins was tested in an in vitro newlineassay. newlineThe thesis is divided into four chapters and the contents of each chapter, in brief, newlineare given below.