Carrier of Wingless (Cow), a secreted heparan sulfate proteoglycan, promotes extracellular transport of Wingless

Yung-Heng Chang; Yi Henry Sun

doi:10.1371/journal.pone.0111573

Carrier of Wingless (Cow), a secreted heparan sulfate proteoglycan, promotes extracellular transport of Wingless

PLoS One. 2014 Oct 31;9(10):e111573. doi: 10.1371/journal.pone.0111573. eCollection 2014.

Authors

Yung-Heng Chang¹, Yi Henry Sun¹

Affiliation

¹ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.

Abstract

Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Drosophila Proteins / metabolism*
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism*
Endocytosis
Epistasis, Genetic
Extracellular Space / metabolism*
Fluorescence Recovery After Photobleaching
Gene Expression Regulation, Developmental
Green Fluorescent Proteins / metabolism
Heparan Sulfate Proteoglycans / metabolism*
Humans
Protein Binding
Protein Stability
Protein Transport
Wnt1 Protein / metabolism*

Substances

Cow protein, Drosophila
Drosophila Proteins
Heparan Sulfate Proteoglycans
Wnt1 Protein
wg protein, Drosophila
Green Fluorescent Proteins

Grants and funding

YHS is supported by grants from Academia Sinica, Taiwan, Republic of China (AS-91-IMB-4PP, AS-95-TP-B04; http://www.sinica.edu.tw/index.shtml), and National Science Council, Taiwan, Republic of China (NSC 96-2321-B-001-002, NSC 97-2321-B-001-002, NSC 98-2321-B-001-034, NSC 99-2321-B-001-016, NSC 100-2321-B-001-012; http://www.most.gov.tw/mp.aspx?mp=7). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.