PMID- 23431147
OWN - NLM
STAT- MEDLINE
DCOM- 20130502
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 110
IP  - 10
DP  - 2013 Mar 5
TI  - Avalanche-like behavior in ciliary import.
PG  - 3925-30
LID - 10.1073/pnas.1217354110 [doi]
AB  - Cilia and flagella are microtubule-based organelles that protrude from the cell 
      body. Ciliary assembly requires intraflagellar transport (IFT), a motile system 
      that delivers cargo from the cell body to the flagellar tip for assembly. The 
      process controlling injections of IFT proteins into the flagellar compartment is, 
      therefore, crucial to ciliogenesis. Extensive biochemical and genetic analyses 
      have determined the molecular machinery of IFT, but these studies do not explain 
      what regulates IFT injection rate. Here, we provide evidence that IFT injections 
      result from avalanche-like releases of accumulated IFT material at the flagellar 
      base and that the key regulated feature of length control is the recruitment of 
      IFT material to the flagellar base. We used total internal reflection 
      fluorescence microscopy of IFT proteins in live cells to quantify the size and 
      frequency of injections over time. The injection dynamics reveal a power-law 
      tailed distribution of injection event sizes and a negative correlation between 
      injection size and frequency, as well as rich behaviors such as quasiperiodicity, 
      bursting, and long-memory effects tied to the size of the localized load of IFT 
      material awaiting injection at the flagellar base, collectively indicating that 
      IFT injection dynamics result from avalanche-like behavior. Computational models 
      based on avalanching recapitulate observed IFT dynamics, and we further show that 
      the flagellar Ras-related nuclear protein (Ran) guanosine 5'-triphosphate (GTP) 
      gradient can in theory act as a flagellar length sensor to regulate this 
      localized accumulation of IFT. These results demonstrate that a self-organizing, 
      physical mechanism can control a biochemically complex intracellular transport 
      pathway.
FAU - Ludington, William B
AU  - Ludington WB
AD  - Department of Biochemistry and Biophysics, University of California, San 
      Francisco, CA 94158, USA.
FAU - Wemmer, Kimberly A
AU  - Wemmer KA
FAU - Lechtreck, Karl F
AU  - Lechtreck KF
FAU - Witman, George B
AU  - Witman GB
FAU - Marshall, Wallace F
AU  - Marshall WF
LA  - eng
GR  - R01 GM097017/GM/NIGMS NIH HHS/United States
GR  - R37 GM030626/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130219
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Plant Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Biological Transport, Active
MH  - Chlamydomonas reinhardtii/genetics/*physiology
MH  - Cilia/*physiology
MH  - Flagella/physiology
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Kinesins/genetics/metabolism
MH  - Microscopy, Fluorescence
MH  - Microscopy, Video
MH  - Models, Biological
MH  - Plant Proteins/genetics/metabolism
PMC - PMC3593837
COIS- The authors declare no conflict of interest.
EDAT- 2013/02/23 06:00
MHDA- 2013/05/03 06:00
PMCR- 2013/02/19
CRDT- 2013/02/23 06:00
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/05/03 06:00 [medline]
PHST- 2013/02/19 00:00 [pmc-release]
AID - 1217354110 [pii]
AID - 201217354 [pii]
AID - 10.1073/pnas.1217354110 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3925-30. doi: 
      10.1073/pnas.1217354110. Epub 2013 Feb 19.