PMID- 18573344 OWN - NLM STAT- MEDLINE DCOM- 20081029 LR - 20211203 IS - 1095-9327 (Electronic) IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 39 IP - 1 DP - 2008 Sep TI - A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons. PG - 63-73 LID - 10.1016/j.mcn.2008.05.016 [doi] AB - Anterograde transport of brain-derived neurotrophic factor (BDNF) vesicles from the soma to neurite terminals is necessary for activity-dependent secretion of BDNF to mediate synaptic plasticity, memory and learning, and retrograde BDNF transport back to the soma for recycling. In our study, overexpression of the cytoplasmic tail of the carboxypeptidase E (CPE) found in BDNF vesicles significantly reduced localization of BDNF in neurites of hippocampal neurons. Live-cell imaging showed that the velocity and distance of movement of fluorescent protein-tagged CPE- or BDNF-containing vesicles were reduced in both directions. In pulldown assays, the CPE tail interacted with dynactin along with kinesin-2 and kinesin-3, and cytoplasmic dynein. Competition assays using a CPE tail peptide verified specific interaction between the CPE tail and dynactin. Thus, the CPE cytoplasmic tail binds dynactin that recruits kinesins or dynein for driving bi-directional transport of BDNF vesicle to maintain vesicle homeostasis and secretion in hippocampal neurons. FAU - Park, Joshua J AU - Park JJ AD - Section on Cellular Neurobiology, Developmental Neurobiology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA. FAU - Cawley, Niamh X AU - Cawley NX FAU - Loh, Y Peng AU - Loh YP LA - eng GR - Z01 HD000056-32/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20080604 PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Isoforms) RN - 0 (Recombinant Fusion Proteins) RN - EC 3.4.17.10 (Carboxypeptidase H) RN - EC 3.6.4.2 (Dyneins) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Animals MH - Biological Transport MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Carboxypeptidase H/chemistry/genetics/*metabolism MH - Dyneins/genetics/metabolism MH - Hippocampus/*cytology/metabolism MH - Homeostasis MH - Kinesins/genetics/metabolism MH - Mice MH - Neurons/cytology/*metabolism MH - Protein Isoforms/genetics/metabolism MH - Rats MH - Recombinant Fusion Proteins/genetics/metabolism MH - Synaptic Vesicles/*metabolism PMC - PMC2606928 MID - NIHMS68985 EDAT- 2008/06/25 09:00 MHDA- 2008/10/31 09:00 PMCR- 2009/09/01 CRDT- 2008/06/25 09:00 PHST- 2008/03/14 00:00 [received] PHST- 2008/05/12 00:00 [revised] PHST- 2008/05/22 00:00 [accepted] PHST- 2008/06/25 09:00 [pubmed] PHST- 2008/10/31 09:00 [medline] PHST- 2008/06/25 09:00 [entrez] PHST- 2009/09/01 00:00 [pmc-release] AID - S1044-7431(08)00138-3 [pii] AID - 10.1016/j.mcn.2008.05.016 [doi] PST - ppublish SO - Mol Cell Neurosci. 2008 Sep;39(1):63-73. doi: 10.1016/j.mcn.2008.05.016. Epub 2008 Jun 4.