Recombinant Human Artemin Protein

Human Artemin (ARTN; also known as enovin and neublastin) is a GDNF family ligand that is distantly related to the TGF-beta superfamily of molecules (1-4). As such, it is synthesized as a preproprotein, and contains a variable length pre-, or signal sequence, plus a 68 amino acid (aa) proregion and a 113 aa mature segment (5-7). Alternate splicing and start sites create signal sequences of 22, 30 and 39 aa, respectively. Their significance is unknown. Following synthesis and proteolytic processing, mature ARTN is secreted as a presumably glycosylated, 28 kDa disulfide-linked homodimer that contains three intrachain disulfide bonds and the typical TGF-beta signature cysteine-knot motif (5, 7). In the mature region, human ARTN is 89% and 88% aa identical to rat (8) and mouse ARTN (5, 7), respectively. Cells known to express ARTN include Schwann cells (2) and embryonic vascular smooth muscle cells (9). Human ARTN is active on rodent cells (5). The receptor for ARTN has been identified as the ligand binding subunit GFR alpha-3 plus the signal transducing subunit, RET (1, 5). The GFR alpha-1/RET receptor complex has also been suggested to be a ligand binding unit for ARTN (2, 5). Evidence, however, suggests that the GFR alpha-1/RET complex plays no functional role in ARTN activity (10, 11). ARTN is known to be a chemoattractant for sympathetic neuron axons innervating the developing cardiovascular system (9). It also promotes sensory neuron survival and likely plays a role in the development of the peripheral nervous system (5). Finally, it has been reported to reverse neuropathic pain due to nerve injury, and to help resolve morphological changes associated with nerve damage (12).