PMID- 31577529
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20200615
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 30
IP  - 23
DP  - 2019 Nov 1
TI  - Septin 2/6/7 complexes tune microtubule plus-end growth and EB1 binding in a 
      concentration- and filament-dependent manner.
PG  - 2913-2928
LID - 10.1091/mbc.E19-07-0362 [doi]
AB  - Septins (SEPTs) are filamentous guanosine-5'-triphosphate (GTP)-binding proteins, 
      which affect microtubule (MT)-dependent functions including membrane trafficking 
      and cell division, but their precise role in MT dynamics is poorly understood. 
      Here, in vitro reconstitution of MT dynamics with SEPT2/6/7, the minimal subunits 
      of septin heteromers, shows that SEPT2/6/7 has a biphasic concentration-dependent 
      effect on MT growth. Lower concentrations of SEPT2/6/7 enhance MT plus-end growth 
      and elongation, while higher and intermediate concentrations inhibit and pause 
      plus-end growth, respectively. We show that SEPT2/6/7 has a modest preference for 
      GTP- over guanosine diphosphate (GDP)-bound MT lattice and competes with 
      end-binding protein 1 (EB1) for binding to guanosine 5'-O-[gamma-thio]triphosphate 
      (GTPgammaS)-stabilized MTs, which mimic the EB1-preferred GDP-Pi state of polymerized 
      tubulin. Strikingly, SEPT2/6/7 triggers EB1 dissociation from plus-end tips in 
      cis by binding to the MT lattice and in trans when MT plus ends collide with 
      SEPT2/6/7 filaments. At these intersections, SEPT2/6/7 filaments were more potent 
      barriers than actin filaments in pausing MT growth and dissociating EB1 in vitro 
      and in live cells. These data demonstrate that SEPT2/6/7 complexes and filaments 
      can directly impact MT plus-end growth and the tracking of plus end-binding 
      proteins and thereby may facilitate the capture of MT plus ends at intracellular 
      sites of septin enrichment.
FAU - Nakos, Konstantinos
AU  - Nakos K
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Radler, Megan R
AU  - Radler MR
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
FAU - Spiliotis, Elias T
AU  - Spiliotis ET
AD  - Department of Biology, Drexel University, Philadelphia, PA 19104.
LA  - eng
GR  - R01 GM097664/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191002
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (EB1 microtubule binding proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - EC 3.6.1.- (Septins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Microtubule-Associated Proteins/*metabolism
MH  - Microtubules/*metabolism
MH  - Models, Biological
MH  - Multiprotein Complexes/*metabolism
MH  - Protein Binding
MH  - Rats, Sprague-Dawley
MH  - Septins/*metabolism
PMC - PMC6822581
EDAT- 2019/10/03 06:00
MHDA- 2020/06/17 06:00
PMCR- 2020/01/16
CRDT- 2019/10/03 06:00
PHST- 2019/10/03 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2019/10/03 06:00 [entrez]
PHST- 2020/01/16 00:00 [pmc-release]
AID - E19-07-0362 [pii]
AID - 10.1091/mbc.E19-07-0362 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2019 Nov 1;30(23):2913-2928. doi: 10.1091/mbc.E19-07-0362. Epub 
      2019 Oct 2.