Slit2 (C fragment) (human) (rec.)

The Slits are secreted proteins that bind to Robo receptors and play a role in axon guidance and neuronal migration. The Slit family in mice and humans comprises three members: Slit1, Slit2 and Slit3. These are all extracellular matrix proteins of 180-200kDa. In vivo, Slit2 is cleaved into 140kDa N-terminal (Slit2-N) and 55-60 kDa C-terminal (Slit2-C) fragments. Only Slit2-N and Slit2 full-length bind the Robo proteins. Recently, it has been shown that Slit2 is highly expressed in adipose tissues under the control of PRDM16 and cold exposure. Slit2 is posttranslationally cleaved by adipocytes and the resulting Slit2-C fragment improves glucose homeostasis in mice by activating a thermogenic PKA/cAMP pathway not mediated by beta-adrenergic receptors in adipocytes. Protein function: Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth- stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal chord midline post- crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration. [The UniProt Consortium]