Syntabulin-mediated anterograde transport of mitochondria along neuronal processes.
In neurons, proper distribution of mitochondria in axons and at synapses is critical for neurotransmission, synaptic plasticity, and axonal outgrowth. However, mechanisms underlying mitochondrial trafficking throughout the long neuronal processes have remained elusive. Here, we report that syntabulin plays a critical role in mitochondrial trafficking in neurons. Syntabulin is a peripheral membrane-associated protein that targets to mitochondria through its carboxyl-terminal tail. Using real-time imaging in living cultured neurons, we demonstrate that a significant fraction of syntabulin colocalizes and co-migrates with mitochondria along neuronal processes. Knockdown of syntabulin expression with targeted small interfering RNA or interference with the syntabulin-kinesin-1 heavy chain interaction reduces mitochondrial density within axonal processes by impairing anterograde movement of mitochondria. These findings collectively suggest that syntabulin acts as a linker molecule that is capable of attaching mitochondrial organelles to the microtubule-based motor kinesin-1, and in turn, contributes to anterograde trafficking of mitochondria to neuronal processes.
Cai
Qian
Q
Synaptic Function Unit, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Gerwin
Claudia
C
Sheng
Zu-Hang
ZH
D000818:Animals; D001369:Axons / Q000378:metabolism; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D016547:Kinesins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D015415:Biomarkers; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C505283:Sybu protein, rat; D049452:Green Fluorescent Proteins; D016547:Kinesins