Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation.
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.
Kang
Jian-Sheng
JS
Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 3B203, 35 Convent Drive, Bethesda, MD 20892, USA.
Tian
Jin-Hua
JH
Pan
Ping-Yue
PY
Zald
Philip
P
Li
Cuiling
C
Deng
Chuxia
C
Sheng
Zu-Hang
ZH
D000818:Animals; D000831:Animals, Newborn; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D033921:Vesicular Transport Proteins / Q000235:genetics*
D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C405513:SNPH protein, human; C527531:Snph protein, mouse; D033921:Vesicular Transport Proteins