Cytoskeletal proteins connecting intermediate filaments to cytoplasmic and nuclear periphery

Abstract

Intermediate filaments (IFS), together with microtubules and microfilaments build up the cytoskeleton of most eukaryotic cells. Cytoplasmic IFS form a dense filament network radiating from the nucleus and extending to the plasma membrane. The association between the cytoplasmic and nuclear surfaces appears to provide a continuous link important for the organisation of the cytoplasm, for cellular communication, and possibly for the transport into and out of the nucleus. Cytoplasmic IFS approach the nuclear surface, thin fibrils seem to connect the IFS with the nuclear pore complexes and a direct interaction of cytoplasmic IFS with the nuclear lamin B has been observed by in vitro binding studies. However, none of the components that cross-link IFS to the nucleus has been unambiguously identified. Furthermore, if a direct interaction between cytoplasmic IFS and the nuclear lamin B occurs in vivo, the question of how cytoplasmic IFS get access to the nuclear interior remains to be resolved. The association of IFS with the plasma membranes involves different components, some of which are cell type specific. Two specialised complexes in epithelia1 cells: the desmosome and the hemidesmosome, serve as attachment sites for keratin filaments. Desmoplakin is considered as the cross-linking component of IFS to the desmosomal plaque, whereas BPAGl (bullous pemphigoid antigen) would cross-link IFS at the hemidesmosomal plaque. In other cell types the modality of how IFS are anchored to the plasma membrane is less well understood. It involves different components such as the spectrin based membrane skeleton, ankyrin, myosin, plectin and certainly many other still unravelled partners. Association between the IFS and cellular membranes plays an important role in determining cell shape and tissue integrity. Thus, the identification and characterisation of the components involved in these interactions will be crucial for understanding the function of intermediate filaments.