Molecular Brain Research 117 (2003) 228–236 www.elsevier.com / locate / molbrainres Short communication Aplysia mollusk-derived growth factor is a mitogen with adenosine deaminase activity and is expressed in the developing central nervous system a,b a,c d d David-Benjamin G. Akalal , Jane E. Bottenstein , Seung-Hee Lee , Jin-Hee Han , Deog- d d a,b, * Jin Chang , Bong-Kiun Kaang , Gregg T. Nagle a Marine Biomedical Institute, University of Texas Medical Branch, Galveston, TX 77555, USA b Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, TX 77555, USA c Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555, USA d National Research Laboratory, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, South Korea Accepted 24 June 2003 Abstract Mollusk-derived growth factor (MDGF), the first growth factor to be characterized in Aplysia, was purified and characterized and has both adenosine deaminase activity and stimulates cell proliferation in vitro. MDGF is structurally related to a new subfamily of adenosine deaminase-related growth factors that require enzymatic activity to stimulate cell proliferation, a unique property of known growth factors. We examined the expression of MDGF protein in the CNS since MDGF mRNA increased in the developing CNS, and recent data suggest that inosine is involved in neuronal reorganization and restoration of essential circuitry after CNS injury. MDGF levels transiently increased during embryonic and post-metamorphic development and in the developing CNS, but was undetectable in adult CNS. No effects on morphology or neurite extension of adult Aplysia neurons were observed.  2003 Elsevier B.V. All rights reserved. Theme: Neurotransmitters, modulators, transporters, and receptors Topic: Transmitters in invertebrates Keywords: ADA; Adenosine deaminase-related growth factor; Aplysia; Developing central nervous system; Insect-derived growth factor; MDGF; CECR1 Growth factors involved in cell proliferation and dif- conditioned medium of an insect cell line stimulates the ferentiation have a wide distribution in vertebrates and proliferation of embryonic NIH-Sape-4 cells from the fly invertebrates, and studies with invertebrate models have Sarcophaga in an autocrine manner [29]. IDGF is present provided insights into complex mechanisms of growth in unfertilized mature eggs and is maintained throughout factor signaling [12,21,24,49]. However, attempts to purify embryonic development, suggesting that it might be a and characterize endogenous growth factors in Aplysia maternal protein important for early embryonic develop- have been largely unsuccessful. To date, only two mollus- ment. IDGF showed no significant homology to other can neurotrophic factors have been purified and character- proteins in the database except for Aplysia atrial gland ized: Lymnaea cysteine-rich neurotrophic factor [22] and granule-specific antigen (AGSA), a glycoprotein that was Lymnaea epidermal growth factor (L-EGF) [25,26,56]. initially thought to play a role in the structure and function An insect-derived growth factor (IDGF) purified from of the cortex of secretory granules [54]. We recently characterized an atrial gland cDNA for AGSA that led to a correction in the sequence, and *Corresponding author. Marine Biomedical Institute, Medical Research renamed the predicted protein mollusk-derived growth Building, Room 2.138, University of Texas Medical Branch, Galveston, factor (MDGF) to emphasize its increased homology to TX 77555, USA. Tel.: 11-409-772-2834; fax: 11-409-772-2789. E-mail address: gtnagle@utmb.edu (G.T. Nagle). IDGF [6]. MDGF mRNA increased markedly in the 0169-328X / 03 / $ – see front matter  2003 Elsevier B.V. All rights reserved. doi:10.1016 / S0169-328X(03)00287-0