Structural insights into the function of Semaphorin4D in neuronal and immune systems
Structural Insights into the Function of Semaphorin4D in Neuronal and Immune Systems Christopher A. Love School of Biomolecular and Biomedical Science & Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Qld, Australia. Abstract Semaphorins are a large family of secreted and transmembrane proteins required for guidance of pioneering axons to their predestined targets during neuronal development. Acting as inhibitors, chemo-repellents or attractants, semaphorins appear to affect axon steering, fasciculation, branching and synapse formation. Research into the function of semaphorins in non-neuronal systems has highlighted the important roles these molecules play in the immune system as well as in organogenesis, vascularisation and angiogenesis. Semaphorins have also been implicated in neurodegenerative diseases such as Parkinson's disease, and in the progression of certain types of cancer. The role of the leukocyte semaphorin, semaphorin4D (Sema4D) is the focus of these studies. Sema4D is a 150 kDa transmembrane protein expressed on the surface of most haemopoietic cells including B and T lymphocytes, and is reportedly involved in T-cell activation. It is one of only a few semaphorin family members known to play a physiological role in the immune system. Described here are insights into Sema4D structure and interaction with its receptors (plexins, neuropilins and CD72). Having determined the structure of Sema4D, studies are underway to solve the structure of its receptor, PlexinB1, and the Sema4D-plexinB1 complex. However, due to the difficulty of crystallising these molecules, other semaphorins (Sema4A), and plexins (PlexinB3), are also being investigated. Aside from the structural studies, the functions of several aspects of Sema4D are of interest and include: (1) the specific role of the PSI domain of Sema4D; (2) mapping of the Sema4D-plexinB1 binding region; and (3) a search for other molecules that interact with Sema4D.
Proceedings of the Australian Society for Biochemistry and Molecular Biology