PMID- 15635594 OWN - NLM STAT- MEDLINE DCOM- 20050418 LR - 20161124 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 79 IP - 4 DP - 2005 Feb 15 TI - Transport of neurofilaments in growing axons requires microtubules but not actin filaments. PG - 442-50 AB - Neurofilament (NF) polymers are conveyed from cell body to axon tip by slow axonal transport, and disruption of this process is implicated in several neuronal pathologies. This movement occurs in both anterograde and retrograde directions and is characterized by relatively rapid but brief movements of neurofilaments, interrupted by prolonged pauses. The present studies combine pharmacologic treatments that target actin filaments or microtubules with imaging of NF polymer transport in living axons to examine the dependence of neurofilament transport on these cytoskeletal systems. The heavy NF subunit tagged with green fluorescent protein was expressed in cultured sympathetic neurons to visualize NF transport. Depletion of axonal actin filaments by treatment with 5 microM latrunculin for 6 hr had no detectable effect on directionality or transport rate of NFs, but frequency of movement events was reduced from 1/3.1 min of imaging time to 1/4.9 min. Depolymerization of axonal microtubules using either 5 microM vinblastine for 3 hr or 5 microg/ml nocodazole for 4-6 hr profoundly suppressed neurofilament transport. In 92% of treated neurons, NF transport was undetected. These observations indicate that actin filaments are not required for neurofilament transport, although they may have subtle effects on neurofilament movements. In contrast, axonal transport of NFs requires microtubules, suggesting that anterograde and retrograde NF transport is powered by microtubule-based motors. CI - Copyright (c) 2005 Wiley-Liss, Inc. FAU - Francis, Franto AU - Francis F AD - Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. FAU - Roy, Subhojit AU - Roy S FAU - Brady, Scott T AU - Brady ST FAU - Black, Mark M AU - Black MM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Neurofilament Proteins) RN - 0 (Thiazoles) RN - 0 (Thiazolidines) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 5V9KLZ54CY (Vinblastine) RN - SH1WY3R615 (Nocodazole) RN - SRQ9WWM084 (latrunculin A) SB - IM MH - Actin Cytoskeleton/*physiology MH - Animals MH - Animals, Newborn MH - Axons/drug effects/*physiology MH - Bridged Bicyclo Compounds, Heterocyclic/pharmacology MH - Diagnostic Imaging/methods MH - Fluorescent Antibody Technique/methods MH - Green Fluorescent Proteins/metabolism MH - Microtubules/*physiology MH - Neurofilament Proteins/*metabolism MH - Neurons/drug effects/*physiology MH - Nocodazole/pharmacology MH - Protein Transport/physiology MH - Rats MH - Superior Cervical Ganglion/cytology MH - Thiazoles/pharmacology MH - Thiazolidines MH - Time Factors MH - Transfection/methods MH - Vinblastine/pharmacology EDAT- 2005/01/07 09:00 MHDA- 2005/04/19 09:00 CRDT- 2005/01/07 09:00 PHST- 2005/01/07 09:00 [pubmed] PHST- 2005/04/19 09:00 [medline] PHST- 2005/01/07 09:00 [entrez] AID - 10.1002/jnr.20399 [doi] PST - ppublish SO - J Neurosci Res. 2005 Feb 15;79(4):442-50. doi: 10.1002/jnr.20399.