Slit1 is a member of the Slit family of large secreted axon guidance molecules that are ligands for Robo receptors (1, 2). Like other mammalian family members, the 1531 amino acid (aa), ~200 kDa Slit1 contains a 33 aa signal sequence followed by 23 leucine rich repeats (LRR, aa 34 900) and 9 EGF like sequences (aa 930 1451) (2). Mammalian Slits also contain a laminin G domain between EGF6 and EGF7 (aa 1163 1336), and a C-terminal cysteine rich domain (cysteine knot; aa 1456 1531)(2). Heparin sulfates are required for interaction of Robo with Slit LRR domains (2, 3). Mouse Slit1 shares 99, 96, 89, 87 and 80% aa identity with rat, human, canine, Xenopus and zebrafish Slit1, respectively, within the LRR domains. Mouse Slits 1, 2 and 3 share 68 74% aa identity within the LRR domains. Slit1 and Slit2 (or in some cases Slit3) are expressed in complementary locations during development of the optic and olfactory tracts and the forebrain, and appear to work together to mediate Robo guidance of retinal, olfactory, hippocampal and motor axons (1, 4, 9).
Deletion of either Slit1 or Slit2 has less effect than deletion of both, which allows axons to wander from tracts and inappropriately cross or recross the midline (4, 5, 7 9). In the injured spinal cord, presence of Slit1 along with Slit3 and Netrin1 may be responsible for failure of axons to regenerate in the adult CNS (10). Slit1 also promotes dendrite growth and branching of cortical neurons indicating it may exert important influence on the final morphology of cortical neurons (11). Although Slit1 has mainly been found in the fetal and adult brain, it is also detected in the heart and kidney. The C-terminal cysteine knot, which may mediate interaction with other proteins, is absent in the rat brain splicing variant, Slit1α (12).
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