PMID- 21363889 OWN - NLM STAT- MEDLINE DCOM- 20110719 LR - 20211203 IS - 1477-9137 (Electronic) IS - 0021-9533 (Linking) VI - 124 IP - Pt 7 DP - 2011 Apr 1 TI - Differential roles of kinesin and dynein in translocation of neurofilaments into axonal neurites. PG - 1022-31 LID - 10.1242/jcs.079046 [doi] AB - Neurofilament (NF) subunits translocate within axons as short NFs, non-filamentous punctate structures ('puncta') and diffuse material that might comprise individual subunits and/or oligomers. Transport of NFs into and along axons is mediated by the microtubule (MT) motor proteins kinesin and dynein. Despite being characterized as a retrograde motor, dynein nevertheless participates in anterograde NF transport through associating with long MTs or the actin cortex through its cargo domain; relatively shorter MTs associated with the motor domain are then propelled in an anterograde direction, along with any linked NFs. Here, we show that inhibition of dynein function, through dynamitin overexpression or intracellular delivery of anti-dynein antibody, selectively reduced delivery of GFP-tagged short NFs into the axonal hillock, with a corresponding increase in the delivery of puncta, suggesting that dynein selectively delivered short NFs into axonal neurites. Nocodazole-mediated depletion of short MTs had the same effect. By contrast, intracellular delivery of anti-kinesin antibody inhibited anterograde transport of short NFs and puncta to an equal extent. These findings suggest that anterograde axonal transport of linear NFs is more dependent upon association with translocating MTs (which are themselves translocated by dynein) than is transport of NF puncta or oligomers. FAU - Lee, Sangmook AU - Lee S AD - Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts, One University Avenue, Lowell, MA 01854, USA. FAU - Sunil, Neethu AU - Sunil N FAU - Tejada, Jennifer Motil AU - Tejada JM FAU - Shea, Thomas B AU - Shea TB LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20110301 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Neurofilament Proteins) RN - EC 3.6.4.2 (Dyneins) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Animals MH - Axonal Transport MH - Cell Line MH - Dyneins/genetics/*metabolism MH - Kinesins/genetics/*metabolism MH - Mice MH - Microtubules/metabolism MH - Neurites/*metabolism MH - Neurofilament Proteins/genetics/*metabolism MH - Protein Transport EDAT- 2011/03/03 06:00 MHDA- 2011/07/20 06:00 CRDT- 2011/03/03 06:00 PHST- 2011/03/03 06:00 [entrez] PHST- 2011/03/03 06:00 [pubmed] PHST- 2011/07/20 06:00 [medline] AID - jcs.079046 [pii] AID - 10.1242/jcs.079046 [doi] PST - ppublish SO - J Cell Sci. 2011 Apr 1;124(Pt 7):1022-31. doi: 10.1242/jcs.079046. Epub 2011 Mar 1.