title: Genetic deletion of trkB.T1 increases neuromuscular function.
abstract: Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB (trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1(-/-) animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.
authors.affiliation: University of Maryland Baltimore School of Nursing, Baltimore, Maryland 21201, USA. sdorsey@son.umaryland.edu
authors.forename: Susan G
authors.initials: SG
authors.lastname: Dorsey
authors.forename: Richard M
authors.initials: RM
authors.lastname: Lovering
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Renn
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Leitch
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liu
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Tallon
authors.forename: Lisa DeShong
authors.initials: LD
authors.lastname: Sadzewicz
authors.forename: Abhishek
authors.initials: A
authors.lastname: Pratap
authors.forename: Sandra
authors.initials: S
authors.lastname: Ott
authors.forename: Naomi
authors.initials: N
authors.lastname: Sengamalay
authors.forename: Kristie M
authors.initials: KM
authors.lastname: Jones
authors.forename: Colleen
authors.initials: C
authors.lastname: Barrick
authors.forename: Gianluca
authors.initials: G
authors.lastname: Fulgenzi
authors.forename: Jodi
authors.initials: J
authors.lastname: Becker
authors.forename: Kevin
authors.initials: K
authors.lastname: Voelker
authors.forename: Robert
authors.initials: R
authors.lastname: Talmadge
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Wyatt
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Vernon-Pitts
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Kevan
authors.initials: K
authors.lastname: Shokat
authors.forename: Claire
authors.initials: C
authors.lastname: Fraser-Liggett
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Balice-Gordon
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ward
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology; D009469:Neuromuscular Junction / Q000235:genetics* / Q000502:physiology; D020813:Receptor, trkB / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D020813:Receptor, trkB; D002118:Calcium