(96b) The Alpha II Spectrin Stablizes Nuclear Lamina Network

The nuclear envelope consists of double layer membranes, nuclear pore complexes, and an underlying protein structural support, the nuclear lamina network. The nuclear lamins are stiff proteins which make up a majority of the nuclear lamina. Spectrins are a family of cytoskeleton proteins characterized with spring-like elastic structure. The aII spectrin is a ubiquitously expressed spectrin protein in nucleated cells. Recently, more and more evidence showed that aII spectrin is associated with nuclear envelop proteins. But its functional role and mechanical effect to nuclear lamina have not been investigated. In this work, we are interested in how this elastic cytoskeleton protein influence the properties nuclear lamina network. We knocked down aII spectrin from Hela cell and found that lamin A and lamin B network response differently to the loss of aII spectrin. Emerin, a nuclear integral protein mislocalized to cytoplasm due to loss of aII spectrin. Most importantly, the nuclear envelope shown dramatic mechanical weakness after loss of aII spectrin, reflected by micropippet aspiration test, nuclear herniation phenomenon and mitosis induced lamina attenuation, etc. Our results suggest that αII?spectrin stabilizes lamina network and lamina associated protein emerin, and it is an essential component of the nuclear lamina infrastructure.