PMID- 24289819
OWN - NLM
STAT- MEDLINE
DCOM- 20140627
LR  - 20211021
IS  - 1749-8104 (Electronic)
IS  - 1749-8104 (Linking)
VI  - 8
DP  - 2013 Dec 1
TI  - Growth cone-specific functions of XMAP215 in restricting microtubule dynamics and 
      promoting axonal outgrowth.
PG  - 22
LID - 10.1186/1749-8104-8-22 [doi]
AB  - BACKGROUND: Microtubule (MT) regulators play essential roles in multiple aspects 
      of neural development. In vitro reconstitution assays have established that the 
      XMAP215/Dis1/TOG family of MT regulators function as MT 'plus-end-tracking 
      proteins' (+TIPs) that act as processive polymerases to drive MT growth in all 
      eukaryotes, but few studies have examined their functions in vivo. In this study, 
      we use quantitative analysis of high-resolution live imaging to examine the 
      function of XMAP215 in embryonic Xenopus laevis neurons. RESULTS: Here, we show 
      that XMAP215 is required for persistent axon outgrowth in vivo and ex vivo by 
      preventing actomyosin-mediated axon retraction. Moreover, we discover that the 
      effect of XMAP215 function on MT behavior depends on cell type and context. While 
      partial knockdown leads to slower MT plus-end velocities in most cell types, it 
      results in a surprising increase in MT plus-end velocities selective to growth 
      cones. We investigate this further by using MT speckle microscopy to determine 
      that differences in overall MT translocation are a major contributor of the 
      velocity change within the growth cone. We also find that growth cone MT 
      trajectories in the XMAP215 knockdown (KD) lack the constrained co-linearity that 
      normally results from MT-F-actin interactions. CONCLUSIONS: Collectively, our 
      findings reveal unexpected functions for XMAP215 in axon outgrowth and growth 
      cone MT dynamics. Not only does XMAP215 balance actomyosin-mediated axon 
      retraction, but it also affects growth cone MT translocation rates and MT 
      trajectory colinearity, all of which depend on regulated linkages to F-actin. 
      Thus, our analysis suggests that XMAP215 functions as more than a simple MT 
      polymerase, and that in both axon and growth cone, XMAP215 contributes to the 
      coupling between MTs and F-actin. This indicates that the function and regulation 
      of XMAP215 may be significantly more complicated than previously appreciated, and 
      points to the importance of future investigations of XMAP215 function during MT 
      and F-actin interactions.
FAU - Lowery, Laura Anne
AU  - Lowery LA
FAU - Stout, Alina
AU  - Stout A
FAU - Faris, Anna E
AU  - Faris AE
FAU - Ding, Liya
AU  - Ding L
FAU - Baird, Michelle A
AU  - Baird MA
FAU - Davidson, Michael W
AU  - Davidson MW
FAU - Danuser, Gaudenz
AU  - Danuser G
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA. 
      gaudenz_danuser@hms.harvard.edu.
FAU - Van Vactor, David
AU  - Van Vactor D
LA  - eng
GR  - R01 NS035909/NS/NINDS NIH HHS/United States
GR  - 2R44GM077774/GM/NIGMS NIH HHS/United States
GR  - U01 GM067230/GM/NIGMS NIH HHS/United States
GR  - F32 NS063512/NS/NINDS NIH HHS/United States
GR  - K99 MH095768/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131201
PL  - England
TA  - Neural Dev
JT  - Neural development
JID - 101286574
RN  - 0 (CKAP5 protein, Xenopus)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Xenopus Proteins)
SB  - IM
MH  - Animals
MH  - Axons/metabolism
MH  - Growth Cones/*metabolism
MH  - Microtubule-Associated Proteins/antagonists & inhibitors/*metabolism
MH  - Microtubules/*metabolism
MH  - Xenopus
MH  - Xenopus Proteins/antagonists & inhibitors/*metabolism
PMC - PMC3907036
EDAT- 2013/12/03 06:00
MHDA- 2014/06/28 06:00
PMCR- 2013/12/01
CRDT- 2013/12/03 06:00
PHST- 2013/11/18 00:00 [received]
PHST- 2013/11/21 00:00 [accepted]
PHST- 2013/12/03 06:00 [entrez]
PHST- 2013/12/03 06:00 [pubmed]
PHST- 2014/06/28 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - 1749-8104-8-22 [pii]
AID - 10.1186/1749-8104-8-22 [doi]
PST - epublish
SO  - Neural Dev. 2013 Dec 1;8:22. doi: 10.1186/1749-8104-8-22.