title: Acetylcholinesterase and agrin: different functions, similar expression patterns, multiple roles.
abstract: Acetylcholinesterase (AChE) and agrin play unique functional roles in the neuromuscular junction (NMJ). AChE is a cholinergic and agrin a synaptogenetic component. In spite of their different functions, they share several common features: their targeting is determined by alternative splicing; unlike most other NMJ components they are expressed in both, muscle and motor neuron and both reside on the synaptic basal lamina of the NMJ. Also, both were reported to play various nonjunctional roles. However, while the origin of basal lamina bound agrin is undoubtedly neural, the neural origin of AChE, which is anchored to the basal lamina with collagenic tail ColQ, is elusive. Hypothesizing that motor neuron proteins targeted to the NMJ basal lamina share common temporal pattern of expression, which is coordinated with the formation of basal lamina, we compared expression of agrin isoforms with the expression of AChE-T and ColQ in the developing rat spinal cord at the stages before and after the formation of NMJ basal lamina. Cellular origin of AChE-T and agrin was determined by in situ hybridization and their quantitative levels by RT PCR. We found parallel increase in expression of the synaptogenetic (agrin 8) isoform of agrin and ColQ after the formation of basal lamina supporting the view that ColQ bound AChE and agrin 8 isoform are destined to the basal lamina. Catalytic AChE-T subunit and agrin isoforms 19 and 0 followed different expression patterns. In accordance with the reports of other authors, our investigations also revealed various alternative functions for AChE and agrin. We have already demonstrated participation of AChE in myoblast apoptosis; here we present the evidence that agrin promotes the maturation of heavy myosin chains and the excitation-contraction coupling. These results show that common features of AChE and agrin extend to their capacity to play multiple roles in muscle development.
authors.affiliation: Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Mis
authors.forename: Urska
authors.initials: U
authors.lastname: Matkovic
authors.forename: Sergej
authors.initials: S
authors.lastname: Pirkmajer
authors.forename: Marina
authors.initials: M
authors.lastname: Sciancalepore
authors.forename: Paola
authors.initials: P
authors.lastname: Lorenzon
authors.forename: Tomaz
authors.initials: T
authors.lastname: Mars
authors.forename: Zoran
authors.initials: Z
authors.lastname: Grubic
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics* / Q000502:physiology*; D018171:Agrin / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D056966:Excitation Contraction Coupling; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009046:Motor Neurons / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
chemical_list: D018171:Agrin; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; C548244:ACHE protein, human; D000110:Acetylcholinesterase; C548246:Ache protein, rat; D018995:Myosin Heavy Chains