Artemin Explained

Artemin, also known as enovin or neublastin, is a protein that in humans is encoded by the ARTN gene.^{[1] [2]}

Function

Artemin is a neurotrophic factor in the glial cell line-derived neurotrophic factor family of ligands which are a group of ligands within the TGF-beta superfamily of signaling molecules. GDNFs are unique in having neurotrophic properties and have potential use for gene therapy in neurodegenerative disease. Artemin has been shown in culture to support the survival of a number of peripheral neuron populations and at least one population of dopaminergic CNS neurons. Its role in the PNS and CNS is further substantiated by its expression pattern in the proximity of these neurons. This protein is a ligand for the RET receptor and uses GFR-alpha 3 as a coreceptor.^[1]

Role in Axonal Development

Artemin, along with other GDNF family of ligands, has been implicated in the structural development and plasticity of several types of neurons, including ventral mesencephalic dopaminergic neurons.^[3] Artemin promotes the survival of newly differentiated neurons after they have undergone terminal mitosis. Artemin has also been found to support the survival neurons in later stages of development and can enhance neuron growth better than neural growth factor during later stages of development.^[4] Artemin plays an important role in migration, proliferation, and differentiation of sympathetic neurons during development. However, during target innervation, sympathetic neurons become dependent on neural growth factor for survival support.^[5]

Unlike other secreted guidance cues during development, artemin acts solely as a chemoattractant and never acts as a chemorepellent.^[6] Artemin is expressed in smooth muscle cells and secreted along blood vessels and in cells near sympathetic axonal projections so that the sympathetic axons can reach their target tissue cells.

Further reading

• Rosenblad C, Grønborg M, Hansen C, Blom N, Meyer M, Johansen J, Dagø L, Kirik D, Patel UA, Lundberg C, Trono D, Björklund A, Johansen TE . 6 . In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin . Molecular and Cellular Neurosciences . 15 . 2 . 199–214 . February 2000 . 10673327 . 10.1006/mcne.1999.0817 . 1378559 .
• Zhu DL, Luo DL, Luo G, Wang B, Gao JM . [Artemin and GFRalpha3 expressions and their relevance to perineural invasiveness and metastasis of pancreatic carcinoma] . Nan Fang Yi Ke da Xue Xue Bao = Journal of Southern Medical University . 29 . 3 . 428–32 . March 2009 . 19304517 .
• Silvian L, Jin P, Carmillo P, Boriack-Sjodin PA, Pelletier C, Rushe M, Gong B, Sah D, Pepinsky B, Rossomando A . 6 . Artemin crystal structure reveals insights into heparan sulfate binding . Biochemistry . 45 . 22 . 6801–12 . June 2006 . 16734417 . 10.1021/bi060035x .
• Pandey V, Qian PX, Kang J, Perry JK, Mitchell MD, Yin Z, Wu ZS, Liu DX, Zhu T, Lobie PE . 6 . Artemin stimulates oncogenicity and invasiveness of human endometrial carcinoma cells . Endocrinology . 151 . 3 . 909–20 . March 2010 . 20118197 . 10.1210/en.2009-0979 . free .
• Masure S, Geerts H, Cik M, Hoefnagel E, Van Den Kieboom G, Tuytelaars A, Harris S, Lesage AS, Leysen JE, Van Der Helm L, Verhasselt P, Yon J, Gordon RD . 6 . Enovin, a member of the glial cell-line-derived neurotrophic factor (GDNF) family with growth promoting activity on neuronal cells. Existence and tissue-specific expression of different splice variants . European Journal of Biochemistry . 266 . 3 . 892–902 . December 1999 . 10583383 . 10.1046/j.1432-1327.1999.00925.x . free .
• Fernandez RM, Ruiz-Ferrer M, Lopez-Alonso M, Antiñolo G, Borrego S . Polymorphisms in the genes encoding the 4 RET ligands, GDNF, NTN, ARTN, PSPN, and susceptibility to Hirschsprung disease . Journal of Pediatric Surgery . 43 . 11 . 2042–7 . November 2008 . 18970938 . 10.1016/j.jpedsurg.2008.05.018 .
• Ceyhan GO, Schäfer KH, Kerscher AG, Rauch U, Demir IE, Kadihasanoglu M, Böhm C, Müller MW, Büchler MW, Giese NA, Erkan M, Friess H . 6 . Nerve growth factor and artemin are paracrine mediators of pancreatic neuropathy in pancreatic adenocarcinoma . Annals of Surgery . 251 . 5 . 923–31 . May 2010 . 20395845 . 10.1097/SLA.0b013e3181d974d4 . 6581279 .
• Kang J, Perry JK, Pandey V, Fielder GC, Mei B, Qian PX, Wu ZS, Zhu T, Liu DX, Lobie PE . 6 . Artemin is oncogenic for human mammary carcinoma cells . Oncogene . 28 . 19 . 2034–45 . May 2009 . 19363524 . 10.1038/onc.2009.66 . free .
• Wang X, Baloh RH, Milbrandt J, Garcia KC . Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors . Structure . 14 . 6 . 1083–92 . June 2006 . 16765900 . 10.1016/j.str.2006.05.010 . free .
• Quartu M, Serra MP, Manca A, Mascia F, Follesa P, Del Fiacco M . Neurturin, persephin, and artemin in the human pre- and full-term newborn and adult hippocampus and fascia dentata . Brain Research . 1041 . 2 . 157–66 . April 2005 . 15829225 . 10.1016/j.brainres.2005.02.007 . 35298612 .
• Otsuki K, Uchida S, Watanuki T, Wakabayashi Y, Fujimoto M, Matsubara T, Funato H, Watanabe Y . 6 . Altered expression of neurotrophic factors in patients with major depression . Journal of Psychiatric Research . 42 . 14 . 1145–53 . October 2008 . 18313696 . 10.1016/j.jpsychires.2008.01.010 .
• Naveilhan P, Baudet C, Mikaels A, Shen L, Westphal H, Ernfors P . Expression and regulation of GFRalpha3, a glial cell line-derived neurotrophic factor family receptor . Proceedings of the National Academy of Sciences of the United States of America . 95 . 3 . 1295–300 . February 1998 . 9448325 . 18749 . 10.1073/pnas.95.3.1295 . 1998PNAS...95.1295N . free .

Notes and References

1. Web site: Entrez Gene: artemin.
2. Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM, Milbrandt J . 6 . Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex . Neuron . 21 . 6 . 1291–302 . December 1998 . 9883723 . 10.1016/S0896-6273(00)80649-2 . 18633359 . free .
3. Zihlmann KB, Ducray AD, Schaller B, Huber AW, Krebs SH, Andres RH, Seiler RW, Meyer M, Widmer HR . 6 . The GDNF family members neurturin, artemin and persephin promote the morphological differentiation of cultured ventral mesencephalic dopaminergic neurons . Brain Research Bulletin . 68 . 1–2 . 42–53 . December 2005 . 16325003 . 10.1016/j.brainresbull.2004.10.012 . 31594656 .
4. Andres R, Forgie A, Wyatt S, Chen Q, de Sauvage FJ, Davies AM . Multiple effects of artemin on sympathetic neurone generation, survival and growth . Development . 128 . 19 . 3685–95 . October 2001 . 10.1242/dev.128.19.3685 . 11585795 .
5. Airaksinen MS, Saarma M . The GDNF family: signalling, biological functions and therapeutic value . Nature Reviews. Neuroscience . 3 . 5 . 383–94 . May 2002 . 11988777 . 10.1038/nrn812 . 2480120 .
6. Honma Y, Araki T, Gianino S, Bruce A, Heuckeroth R, Johnson E, Milbrandt J . Artemin is a vascular-derived neurotropic factor for developing sympathetic neurons . Neuron . 35 . 2 . 267–82 . July 2002 . 12160745 . 10.1016/s0896-6273(02)00774-2 . 8104679 . free .