[5] Cobl was demonstrated to be a brain-enriched, Wiskott-Aldrich Homology 2 WH2 domain–based actin nucleator playing a pivotal role in morphogenetic processes in the vertebrate central nervous system (CNS) that give rise to the complex dendritic arbor of neuronal cells.
[10] Cobl mRNA was detected as early as at day 7.5 post-coitum (E7.5) in the gastrula organizer and extended towards the axial midline at E8.
The cobl gene in mice and human gives rise to a variety of putative splice variants, which, however, have not yet been analyzed at the protein level.
[16] The WH2 domain-based actin nucleator Cobl turned out to be critical for the induction of dendritic branches in both hippocampal neurons and Purkinje cells of the cerebellum, as revealed by RNAi experiments.
[5] Interestingly, Ca2+/CaM controls not only the actin cytoskeletal aspects of Cobl functions but also its targeting to the plasma membrane - a prerequisite for F-actin-driven force generation shaping the morphology of cells.
[6][7] Also binding sites for profilin-actin heterodimers have been suggested, selected Ser residues are phosphorylated and two Arginines in the second WH2 domain, which is considered the pace maker of the actin nucleation process were detected to be methylated.
In fact already low nanomolar concentrations of Cobl can generate unbranched filaments with similar characteristics as WASp–Arp2/3-complex-mediated actin nucleation.
[5][7] Critical roles of Cobl have also been suggested for microvilli formation of colon cells (Grega-Larson et al.,) and in the organization of sensory systems.
Due to its role in vertebrate neural morphogenesis we can speculate that some neurodegenative disorders may be a consequence of a mutated or less functional Cobl.
Cobl seems to play a role in the skeletal asymmetry of the Silver-Russel syndrome; the disease is caused by the duplication of the p11.2-p13 segment of the chromosome 7.
[21] Screening studies on patients having neurological disorders didn't report until now (June 2009) a specific involvement of Cobl.
[10] Cobl mRNA was detected as early as at day 7.5 post-coitum (E7.5) in the gastrula organizer and extended towards the axial midline at E8.
Cobl knockout mice were viable and showed no obvious defects in neural tube closure and/or body laterality.
Cordon-bleu protein, uses two WH2 motifs (blue segment) for the recruitment of ATP-actin monomers (dark orange) to form a linear actin dimer (Fig.
A short linker (short green segment) permits a close association between the linearly arranged actin subunits; a longer linker (long green segment) permits a third ATP-actin monomer to bind to the most carboxy-terminal WH2 motif to assemble in a cross-filament orientation, creating a trimeric actin nucleus.
Additional four ATP-actin monomers associate laterally along this tetramer to form a short typical two-strand helical actin filament (cf.