PMID- 30120810 OWN - NLM STAT- MEDLINE DCOM- 20190726 LR - 20240402 IS - 1600-0854 (Electronic) IS - 1398-9219 (Print) IS - 1398-9219 (Linking) VI - 19 IP - 11 DP - 2018 Nov TI - T-complex protein 1-ring complex enhances retrograde axonal transport by modulating tau phosphorylation. PG - 840-853 LID - 10.1111/tra.12610 [doi] AB - The cytosolic chaperonin T-complex protein (TCP) 1-ring complex (TRiC) has been shown to exert neuroprotective effects on axonal transport through clearance of mutant Huntingtin (mHTT) in Huntington's disease. However, it is presently unknown if TRiC also has any effect on axonal transport in wild-type neurons. Here, we examined how TRiC impacted the retrograde axonal transport of brain-derived neurotrophic factor (BDNF). We found that expression of a single TRiC subunit significantly enhanced axonal transport of BDNF, leading to an increase in instantaneous velocity with a concomitant decrease in pauses for retrograde BDNF transport. The transport enhancing effect by TRiC was dependent on endogenous tau expression because no effect was seen in neurons from tau knockout mice. We showed that TRiC regulated the level of cyclin-dependent kinase 5 (CDK5)/p35 positively, contributing to TRiC-mediated tau phosphorylation (ptau). Expression of a single TRiC subunit increased the level of ptau while downregulation of the TRiC complex decreased ptau. We further demonstrated that TRiC-mediated increase in ptau induced detachment of tau from microtubules. Our study has thus revealed that TRiC-mediated increase in tau phosphorylation impacts retrograde axonal transport. CI - (c) 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Chen, Xu-Qiao AU - Chen XQ AD - Department of Neurosciences, University of California San Diego, La Jolla, California. FAU - Fang, Fang AU - Fang F AD - Department of Neurosciences, University of California San Diego, La Jolla, California. FAU - Florio, Jazmin B AU - Florio JB AD - Department of Neurosciences, University of California San Diego, La Jolla, California. FAU - Rockenstein, Edward AU - Rockenstein E AD - Department of Neurosciences, University of California San Diego, La Jolla, California. FAU - Masliah, Eliezer AU - Masliah E AD - Department of Neurosciences, University of California San Diego, La Jolla, California. FAU - Mobley, William C AU - Mobley WC AD - Department of Neurosciences, University of California San Diego, La Jolla, California. FAU - Rissman, Robert A AU - Rissman RA AD - Department of Neurosciences, University of California San Diego, La Jolla, California. AD - Veterans Affairs San Diego Healthcare System, San Diego, California. FAU - Wu, Chengbiao AU - Wu C AUID- ORCID: 0000-0002-3660-088X AD - Department of Neurosciences, University of California San Diego, La Jolla, California. AD - Veterans Affairs San Diego Healthcare System, San Diego, California. LA - eng GR - R21 AG051839/AG/NIA NIH HHS/United States GR - P50 AG005131/AG/NIA NIH HHS/United States GR - I01 BX003040/BX/BLRD VA/United States GR - R01 AG051848/AG/NIA NIH HHS/United States GR - R01 AG018440/AG/NIA NIH HHS/United States GR - R37 AG018440/AG/NIA NIH HHS/United States GR - P01 NS092525/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20180912 PL - England TA - Traffic JT - Traffic (Copenhagen, Denmark) JID - 100939340 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (tau Proteins) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) RN - EC 3.6.1.- (Chaperonin Containing TCP-1) MH - Animals MH - *Axonal Transport MH - Brain-Derived Neurotrophic Factor/metabolism MH - CHO Cells MH - Cells, Cultured MH - Chaperonin Containing TCP-1/genetics/*metabolism MH - Cricetinae MH - Cricetulus MH - Cyclin-Dependent Kinase 5/metabolism MH - HEK293 Cells MH - Humans MH - Microtubules/metabolism MH - Phosphorylation MH - Rats MH - tau Proteins/*metabolism PMC - PMC6191364 MID - NIHMS985975 OTO - NOTNLM OT - TRiC/CCT chaperonin OT - axonal transport OT - hyperphosphorylation OT - tau COIS- Conflict of interest The authors declare no conflict of interest. EDAT- 2018/08/19 06:00 MHDA- 2019/07/28 06:00 PMCR- 2019/11/01 CRDT- 2018/08/19 06:00 PHST- 2018/02/07 00:00 [received] PHST- 2018/08/09 00:00 [revised] PHST- 2018/08/12 00:00 [accepted] PHST- 2018/08/19 06:00 [pubmed] PHST- 2019/07/28 06:00 [medline] PHST- 2018/08/19 06:00 [entrez] PHST- 2019/11/01 00:00 [pmc-release] AID - 10.1111/tra.12610 [doi] PST - ppublish SO - Traffic. 2018 Nov;19(11):840-853. doi: 10.1111/tra.12610. Epub 2018 Sep 12.