Disassembly of the NE at prophase correlates with phosphorylation of proteins of the chromatin, nuclear membranes and lamina, leading to solubilization of lamin A/C while B-type lamins remain mostly in a membrane-bound form

The nuclear envelope (NE) is a highly dynamic structure consisting of two concentric membranes underlaid by the nuclear lamina, a network of intermediate filaments called A/Cand B-type lamins (reviewed by Collas and Courvalin, 2000; Wilson, 2000). The outer nuclear membrane (ONM) is in direct continuity with the endoplasmic reticulum (ER) and shares biochemical and functional properties with the ER. The inner nuclear membrane (INM) harbors specific integral proteins that provide attachment sites for chromatin and the nuclear lamina. ONM and INM are connected by sharply bend membranes associated with nuclear pore complexes. The dynamic nature of the NE is best illustrated at mitosis when the NE breaks down and reassembles around daughter chromosomes. Disassembly of the NE at prophase correlates with phosphorylation of proteins of the chromatin, nuclear membranes and lamina, leading to solubilization of lamin A/C while B-type lamins remain mostly in a membrane-bound form (Gerace and Blobel, 1980). In late anaphase, ER-derived membranes associate with chromatin to reform nuclear membranes (Chaudhary and Courvalin, 1993; Ellenberg et al., 1997), while in telophase, lamins are dephosphorylated and repolymerize (Ottaviano and Gerace, 1985). Proteins of the INM, lamina and chromosomes are extensively interconnected. The INM harbors specific integral proteins including lamin B receptor (LBR; Worman et al., 1990), lamina-associated polypeptides (LAP)1 and LAP2 (Foisner and Gerace, 1993), emerin (Nagano et al., 1996), nurim (Rolls et al., 1999) and MAN1 (Lin et al., 2000). LBR, LAP1, LAP2β and emerin bind to lamins A/C and/or B in vitro (reviewed by Wilson, 2000). LBR and LAP2β also bind chromatin via interactions with heterochromatin protein (HP)1 (Ye and Worman, 1996) and the small DNA-binding protein BAF (barrier to autointegration factor; Furukawa, 1999). An intranuclear LAP2 variant, LAP2α, also interacts with lamins A/C (Dechat et al., 1998) while H2-type histones bind lamins A/C and B in vitro (Goldberg et al., 1999). Thus, the chromatin provides multiple anchoring sites for the NE. HA95, also called HAP95 or NAKAP95, is a novel nuclear protein recently cloned by us (Ørstavik et al., 2000) and others (Seki et al., 2000; Westberg et al., 2000). HA95 exhibits high homology to the human nuclear A-kinase (PKA) anchoring protein, AKAP95 (Eide et al., 1998). Like AKAP95, HA95 harbors two zinc fingers and a putative nuclear localization signal but does not contain the PKA-binding domain of AKAP95 (Ørstavik et al., 2000). HA95 and AKAP95 colocalize in interphase and at mitosis, yet the two proteins do 3703 Journal of Cell Science 113, 3703-3713 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 JCS1711