ABSTRACT
The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.
Subject(s)
Axons , Physiology , Nerve Tissue Proteins , Physiology , Receptors, Immunologic , PhysiologyABSTRACT
The axon guidance molecule Slit is a secreted glucoprotein which is conserved during evolution. Slit has been implicated in regulating a variety of life activities, such as axon guidance, neuronal migration, neuronal morphological differentiation, tumor metastasis, angiogenesis and heart morphogenesis. Slit function mainly depends on the binding of its LRR-2 domain to the Ig1 domain of Roundabout (Robo) receptor, meanwhile Slit function is also mediated by a range of signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs), tyrosine kinase Abelson, calcium ions, MicroRNA-218 and other axon guidance molecules. Several transcription factors, including Single-minded, Irx and Midline, were shown to regulate slit expression. In addition, multiple Slit isoforms exist as a consequence of alternative spliced transcripts. The research on guidance mechanism of Slit will facilitate the understanding of molecular mechanism underlying neural networks formation in the process of neural development and regeneration. Meanwhile, the studying of Slit guidance mechanism could promote the prevention and treatment of human neurological diseases and cancer metastasis.