Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration

Jui Hsia Weng; Ming Ren Liang; Chien Han Chen; Sok Keng Tong; Tzu Chiao Huang; Sue Ping Lee; Yet Ran Chen; Chao Tsen Chen; Bon Chu Chung

doi:10.1038/nchembio.1321

Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration

Jui Hsia Weng, Ming Ren Liang, Chien Han Chen, Sok Keng Tong, Tzu Chiao Huang, Sue Ping Lee, Yet Ran Chen, Chao Tsen Chen, Bon Chu Chung

Research output: Contribution to journal › Article › peer-review

40 Citations (Scopus)

Abstract

Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation. This increased CLIP-170 interaction with microtubules, dynactin subunit p150 Glued and LIS1; it also promoted CLIP-170-dependent microtubule polymerization. CLIP-170 was essential for P5 to promote microtubule abundance and zebrafish epiboly cell migration during embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed this migration. P5 also sustained migration directionality of cultured mammalian cells. Our results show that P5 activates CLIP-170 to promote microtubule polymerization and cell migration.

Original language	English
Pages (from-to)	636-642
Number of pages	7
Journal	Nature Chemical Biology
Volume	9
Issue number	10
DOIs	https://doi.org/10.1038/nchembio.1321
Publication status	Published - Oct 2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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10.1038/nchembio.1321

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@article{c729a4b107dc4019b59251b3491e992a,

title = "Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration",

abstract = "Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation. This increased CLIP-170 interaction with microtubules, dynactin subunit p150 Glued and LIS1; it also promoted CLIP-170-dependent microtubule polymerization. CLIP-170 was essential for P5 to promote microtubule abundance and zebrafish epiboly cell migration during embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed this migration. P5 also sustained migration directionality of cultured mammalian cells. Our results show that P5 activates CLIP-170 to promote microtubule polymerization and cell migration.",

author = "Weng, {Jui Hsia} and Liang, {Ming Ren} and Chen, {Chien Han} and Tong, {Sok Keng} and Huang, {Tzu Chiao} and Lee, {Sue Ping} and Chen, {Yet Ran} and Chen, {Chao Tsen} and Chung, {Bon Chu}",

note = "Funding Information: We thank S. Takashima (Osaka University) and N. Galjart (Erasmus Medical Center) for CLIP-170 plasmids, S. Tsukita (Kyoto University) for the EB1-GFP plasmid, S. Halpain (University of California–San Diego) for the MAP2c plasmid and Y. Mimori-Kiyosue (RIKEN) for the GFP-CLIP-115 plasmid, generated by A. Akhmanova (Utrecht University). We thank W.-y. Ku and C.-w. Hsu for help in drawing the graphical abstract. RNAi reagents were obtained from the National RNAi Core Facility Platform at Academia Sinica (NSC 97-3112-B-001-016). The wild-type zebrafish were from Taiwan Zebrafish Core Facility at Academia Sinica (NSC 100-2321-B-001-030). C.-T.C. was supported by the National Science Council (NSC 97-2113-M-002-002-MY3 and NSC99-3112-B-001-002) and the National Taiwan University, and B.-c.C. was supported by the National Science Council (NSC101-2321-B-001-001, NSC 102-2311-B-001-013-MY3), the National Health Research Institute (NHRI-EX102-10210SI) and Academia Sinica.",

year = "2013",

month = oct,

doi = "10.1038/nchembio.1321",

language = "English",

volume = "9",

pages = "636--642",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Publishing Group",

number = "10",

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TY - JOUR

T1 - Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration

AU - Weng, Jui Hsia

AU - Liang, Ming Ren

AU - Chen, Chien Han

AU - Tong, Sok Keng

AU - Huang, Tzu Chiao

AU - Lee, Sue Ping

AU - Chen, Yet Ran

AU - Chen, Chao Tsen

AU - Chung, Bon Chu

N1 - Funding Information: We thank S. Takashima (Osaka University) and N. Galjart (Erasmus Medical Center) for CLIP-170 plasmids, S. Tsukita (Kyoto University) for the EB1-GFP plasmid, S. Halpain (University of California–San Diego) for the MAP2c plasmid and Y. Mimori-Kiyosue (RIKEN) for the GFP-CLIP-115 plasmid, generated by A. Akhmanova (Utrecht University). We thank W.-y. Ku and C.-w. Hsu for help in drawing the graphical abstract. RNAi reagents were obtained from the National RNAi Core Facility Platform at Academia Sinica (NSC 97-3112-B-001-016). The wild-type zebrafish were from Taiwan Zebrafish Core Facility at Academia Sinica (NSC 100-2321-B-001-030). C.-T.C. was supported by the National Science Council (NSC 97-2113-M-002-002-MY3 and NSC99-3112-B-001-002) and the National Taiwan University, and B.-c.C. was supported by the National Science Council (NSC101-2321-B-001-001, NSC 102-2311-B-001-013-MY3), the National Health Research Institute (NHRI-EX102-10210SI) and Academia Sinica.

PY - 2013/10

Y1 - 2013/10

N2 - Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation. This increased CLIP-170 interaction with microtubules, dynactin subunit p150 Glued and LIS1; it also promoted CLIP-170-dependent microtubule polymerization. CLIP-170 was essential for P5 to promote microtubule abundance and zebrafish epiboly cell migration during embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed this migration. P5 also sustained migration directionality of cultured mammalian cells. Our results show that P5 activates CLIP-170 to promote microtubule polymerization and cell migration.

AB - Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation. This increased CLIP-170 interaction with microtubules, dynactin subunit p150 Glued and LIS1; it also promoted CLIP-170-dependent microtubule polymerization. CLIP-170 was essential for P5 to promote microtubule abundance and zebrafish epiboly cell migration during embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed this migration. P5 also sustained migration directionality of cultured mammalian cells. Our results show that P5 activates CLIP-170 to promote microtubule polymerization and cell migration.

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U2 - 10.1038/nchembio.1321

DO - 10.1038/nchembio.1321

M3 - Article

C2 - 23955365

AN - SCOPUS:84884533735

SN - 1552-4450

VL - 9

SP - 636

EP - 642

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 10

ER -

Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration

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