The Roles of Actin-binding Proteins MIM and ABBA1 in the Development of the Central Nervous System

Principal Investigators: PEKKA LAPPALAINEN1, MARJO SALMINEN2

Programs in 1Cellular Biotechnology and 2Developmental Biology, Institute of Biotechnology, University of Helsinki, Finland

Actin is a ubiquitous protein, which forms a major structural component of the cytoskeleton. In skeletal muscle cells the actin filaments that underlie muscle contraction are long-lived and uniform in length, and are organized into nearly crystalline arrays. In contrast, the actin filaments in non-muscle cells are highly dynamic and are closely linked to changes in cell's shape and motility. The actin cytoskeleton also plays an important role in endo- and exocytosis, and intracellular signal transduction. Recent studies have shown that the actin cytoskeleton is also a common target for many signaling cascades that regulate the development and morphogenesis of neuronal cells. Coordinated polymerization and depolymerization of actin filaments are the driving force of axon guidance and growth cone motility. Furthermore, the morphogenesis and plasticity of dendritic spines, the small protrusions that receive excitatory synaptic input along dendrites, are regulated by specific actin filament structures. We have recently identified two cell-type specific mouse actin-binding proteins, MIM and ABBA1, which are composed of similar functional domains. Our Northern blot and in situ hybridization analyzes demonstrated that MIM is strongly expressed in the central nervous system (CNS) neurons during embryogenesis and in adult mice. In contrast to the neuronal expression of MIM, strong ABBA1 expression is confined to specific glial cells of developing and adult CNS. In order to understand the in vivo functions of MIM and ABBA1 during mouse CNS development, we will inactivate the two genes in mouse genome. Furthermore, we will carry out biochemical and cell biological analyses to reveal the mechanisms by which MIM and ABBA1, together with their putative interaction partners, contribute to actin turnover and specific actin-dependent cellular processes in neuronal cells.

Contact: pekka.lappalainen(at)helsinki.fi, tel. +358 9 1915 9499