Drosophila Strip serves as a platform for early endosome organization during axon elongation

Chisako Sakuma; Takeshi Kawauchi; Shuka Haraguchi; Mima Shikanai; Yoshifumi Yamaguchi; Vladimir I. Gelfand; Liqun Luo; Masayuki Miura; Takahiro Chihara

doi:10.1038/ncomms6180

Drosophila Strip serves as a platform for early endosome organization during axon elongation

Chisako Sakuma, Takeshi Kawauchi, Shuka Haraguchi, Mima Shikanai, Yoshifumi Yamaguchi, Vladimir I. Gelfand, Liqun Luo, Masayuki Miura, Takahiro Chihara^*

^*Corresponding author for this work

Cell & Developmental Biology

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

28 Scopus citations

Abstract

Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.

Original language	English (US)
Article number	5180
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6180
State	Published - Oct 14 2014

Funding

We thank D. Bilder, M. González-Gaitán, T. Schwarz, S. X. Hou, the Bloomington Drosophila Stock Centre (NIH P40OD018537), and the Kyoto Drosophila Genetic Resource Centre for fly stocks. We thank T. Vaccari for anti-Avl antibody, M. González-Gaitán for anti-Rab5 antibody, C.-H. Chen for advising us on shRNA construction, Y. Hiromi for actin-Gal4 plasmid and all members of the Miura and Luo laboratories for their comments on this study. L.L. is an investigator in the Howard Hughes Medical Institute. This work was supported by grants from the National Institute of General Medical Science of the National Institutes of Health (R01-GM085232 to V.I.G.), the National Institutes of Health (R01-DC005982 to L.L.), the Japanese Ministry of Education, Science, Sports, Culture, and Technology (MEXT), the Japan Society for the Promotion of Science, and the Japan Science and Technology Agency (to C.S., K.T., Y.Y., M.M., and T.C.).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/ncomms6180

Cite this

@article{fc1d823dbc714cf39f9a229620b25f3d,

title = "Drosophila Strip serves as a platform for early endosome organization during axon elongation",

abstract = "Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.",

author = "Chisako Sakuma and Takeshi Kawauchi and Shuka Haraguchi and Mima Shikanai and Yoshifumi Yamaguchi and Gelfand, {Vladimir I.} and Liqun Luo and Masayuki Miura and Takahiro Chihara",

year = "2014",

month = oct,

day = "14",

doi = "10.1038/ncomms6180",

language = "English (US)",

volume = "5",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - Drosophila Strip serves as a platform for early endosome organization during axon elongation

AU - Sakuma, Chisako

AU - Kawauchi, Takeshi

AU - Haraguchi, Shuka

AU - Shikanai, Mima

AU - Yamaguchi, Yoshifumi

AU - Gelfand, Vladimir I.

AU - Luo, Liqun

AU - Miura, Masayuki

AU - Chihara, Takahiro

PY - 2014/10/14

Y1 - 2014/10/14

N2 - Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.

AB - Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. Strip knockdown disturbs the early endosome clustering, and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip-mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that has important roles in neuronal morphogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84929963761&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929963761&partnerID=8YFLogxK

U2 - 10.1038/ncomms6180

DO - 10.1038/ncomms6180

M3 - Article

C2 - 25312435

AN - SCOPUS:84929963761

SN - 2041-1723

VL - 5

JO - Nature communications

JF - Nature communications

M1 - 5180

ER -

Drosophila Strip serves as a platform for early endosome organization during axon elongation

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this