title: Transglutaminase forms midkine homodimers in cerebellar neurons and modulates the neurite-outgrowth response.
abstract: Midkine is a prominent acyl donor substrate for the protein cross-linking enzyme transglutaminase type 2 in rat brain neurons. Transglutaminase type 2 and midkine immunoreactivity are regionally colocalized in developing cerebellar cortex. Monomeric midkine is present in the embryonic dorsal rhombic lip which gives rise to the cerebellar cortex. A high-molecular weight (29-30 kDa) midkine appears during postnatal cerebellar development. The presence of the high-molecular weight midkine in cultured cerebellar cortical interneurons is dependent upon culture conditions. Transglutaminase catalyzes the calcium-dependent cross-linking of midkine predominantly into 29-30 kDa dimers. Dimer-formation of midkine in vitro and in cultured neurons is reduced in the presence of a transglutaminase inactivator. Neurons plated onto previously cross-linked midkine exhibit larger growth cones and enhanced neurite outgrowth compared to those plated onto monomeric midkine alone.
authors.affiliation: School of Biological Sciences, University of Bristol, England.
authors.forename: S A
authors.initials: SA
authors.lastname: Mahoney
authors.forename: M
authors.initials: M
authors.lastname: Perry
authors.forename: A
authors.initials: A
authors.lastname: Seddon
authors.forename: P
authors.initials: P
authors.lastname: Bohlen
authors.forename: L
authors.initials: L
authors.lastname: Haynes
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016207:Cytokines; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D000078792:Midkine; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D016207:Cytokines; D007527:Isoenzymes; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D000078792:Midkine; D011503:Transglutaminases