Abstract
XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assembly of these arrays into large square complexes. Here, we describe a relationship between MT plus-end tracking and polymerase functions revealing their distinct origin within TOG arrays. We study Alp14 mutants designed based on structural models, with defects in either tubulin recruitment or self-organization. Using in vivo live imaging in fission yeast and in vitro MT dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in MT plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking, whereas TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive MT plus-end tracking and polymerase. Our studies suggest that a dynamic cycle between square and unfurled TOG array states gives rise to processive polymerase activity at MT plus ends.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1490-1504 |
| Number of pages | 15 |
| Journal | Molecular biology of the cell |
| Volume | 30 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 1 2019 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays. / Cook, Brian D.; Chang, Fred; Flor-Parra, Ignacio; Al-Bassam, Jawdat.
In: Molecular biology of the cell, Vol. 30, No. 12, 01.06.2019, p. 1490-1504.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Microtubule polymerase and processive plus-end tracking functions originate from distinct features within TOG domain arrays
AU - Cook, Brian D.
AU - Chang, Fred
AU - Flor-Parra, Ignacio
AU - Al-Bassam, Jawdat
PY - 2019/6/1
Y1 - 2019/6/1
N2 - XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assembly of these arrays into large square complexes. Here, we describe a relationship between MT plus-end tracking and polymerase functions revealing their distinct origin within TOG arrays. We study Alp14 mutants designed based on structural models, with defects in either tubulin recruitment or self-organization. Using in vivo live imaging in fission yeast and in vitro MT dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in MT plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking, whereas TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive MT plus-end tracking and polymerase. Our studies suggest that a dynamic cycle between square and unfurled TOG array states gives rise to processive polymerase activity at MT plus ends.
AB - XMAP215/Stu2/Alp14 accelerates tubulin polymerization while processively tracking microtubule (MT) plus ends via tumor overexpressed gene (TOG) domain arrays. It remains poorly understood how these functions arise from tubulin recruitment, mediated by the distinct TOG1 and TOG2 domains, or the assembly of these arrays into large square complexes. Here, we describe a relationship between MT plus-end tracking and polymerase functions revealing their distinct origin within TOG arrays. We study Alp14 mutants designed based on structural models, with defects in either tubulin recruitment or self-organization. Using in vivo live imaging in fission yeast and in vitro MT dynamics assays, we show that tubulins recruited by TOG1 and TOG2 serve concerted, yet distinct, roles in MT plus-end tracking and polymerase functions. TOG1 is critical for processive plus-end tracking, whereas TOG2 is critical for accelerating tubulin polymerization. Inactivating interfaces that stabilize square complexes lead to defects in both processive MT plus-end tracking and polymerase. Our studies suggest that a dynamic cycle between square and unfurled TOG array states gives rise to processive polymerase activity at MT plus ends.
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UR - http://www.scopus.com/inward/citedby.url?scp=85067266985&partnerID=8YFLogxK
U2 - 10.1091/mbc.E19-02-0093
DO - 10.1091/mbc.E19-02-0093
M3 - Article
C2 - 30969896
AN - SCOPUS:85067266985
VL - 30
SP - 1490
EP - 1504
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 12
ER -