@article{003c6f96c87f492fb7532d6c87b92edc,
title = "Docking of Axonal Mitochondria by Syntaphilin Controls Their Mobility and Affects Short-Term Facilitation",
abstract = "Proper distribution of mitochondria within axons and at synapses is critical for neuronal function. While one-third of axonal mitochondria are mobile, a large proportion remains in a stationary phase. However, the mechanisms controlling mitochondrial docking within axons remain elusive. Here, we report a role for axon-targeted syntaphilin (SNPH) in mitochondrial docking through its interaction with microtubules. Axonal mitochondria that contain exogenously or endogenously expressed SNPH lose mobility. Deletion of the mouse snph gene results in a substantially higher proportion of axonal mitochondria in the mobile state and reduces the density of mitochondria in axons. The snph mutant neurons exhibit enhanced short-term facilitation during prolonged stimulation, probably by affecting calcium signaling at presynaptic boutons. This phenotype is fully rescued by reintroducing the snph gene into the mutant neurons. These findings demonstrate a molecular mechanism for controlling mitochondrial docking in axons that has a physiological impact on synaptic function.",
keywords = "CELLBIO, MOLNEURO",
author = "Kang, {Jian Sheng} and Tian, {Jin Hua} and Pan, {Ping Yue} and Philip Zald and Cuiling Li and Chuxia Deng and Sheng, {Zu Hang}",
note = "Funding Information: We thank the following people for their help: S. Das and C. Smith for the initial identification of mitochondrial targeting of SNPH; R. Youle, L.-G. Wu, J. Diamond, G. Chen, E. Jonas, Q. Cai for helpful discussions; C. Gerwin for critical reading of the manuscript; R.S. Petralia and Y.X. Wang for mice perfusion; Electron Microscopy Facility (National Institute of Neurological Disorders and Stroke [NINDS]) and DNA Sequencing Facility (NINDS). We thank three anonymous reviewers for constructive suggestions to strengthen the study. Behavioral study was conducted by NeuroDetective Inc. under service contract. P.-Y.P. is a graduate student of the NIH-Shanghai JiaoTong University Joint Ph.D. Program in Neuroscience. This work was supported by intramural research program of NINDS, NIH (Z.-H.S.). All animal experiments have been conducted in accordance with the NIH Animal Use Guidelines. Author Contributions: J.-S.K. did the cell biology studies and modeling and wrote the manuscript, J.-H.T. made the KO mice, P.-Y.P performed electrophysiological studies and wrote the manuscript, C.L. and C.D. helped with the generation of KO mice, P.Z. did the initial study of mitochondrial targeting. Z.-H.S. is a senior author who was responsible for the project design and wrote the paper. ",
year = "2008",
month = jan,
day = "11",
doi = "10.1016/j.cell.2007.11.024",
language = "English (US)",
volume = "132",
pages = "137--148",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}