Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing

Anna F. Rives, Kate M. Rochlin, Marcel Wehrli, Stephanie L. Schwartz, Stephen DiNardo

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.

Original languageEnglish (US)
Pages (from-to)268-283
Number of pages16
JournalDevelopmental Biology
Volume293
Issue number1
DOIs
StatePublished - May 1 2006

Fingerprint

Drosophila
Lysosomes
Epidermis
Signal Transduction
hepatocyte growth factor-regulated tyrosine kinase substrate

Keywords

  • Arrow
  • Endocytic trafficking
  • Frizzled-2
  • Wingless

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. / Rives, Anna F.; Rochlin, Kate M.; Wehrli, Marcel; Schwartz, Stephanie L.; DiNardo, Stephen.

In: Developmental Biology, Vol. 293, No. 1, 01.05.2006, p. 268-283.

Research output: Contribution to journalArticle

Rives, Anna F. ; Rochlin, Kate M. ; Wehrli, Marcel ; Schwartz, Stephanie L. ; DiNardo, Stephen. / Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. In: Developmental Biology. 2006 ; Vol. 293, No. 1. pp. 268-283.
@article{dd6368019158459f88c75f7222a39036,
title = "Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing",
abstract = "During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.",
keywords = "Arrow, Endocytic trafficking, Frizzled-2, Wingless",
author = "Rives, {Anna F.} and Rochlin, {Kate M.} and Marcel Wehrli and Schwartz, {Stephanie L.} and Stephen DiNardo",
year = "2006",
month = "5",
day = "1",
doi = "10.1016/j.ydbio.2006.02.006",
language = "English (US)",
volume = "293",
pages = "268--283",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing

AU - Rives, Anna F.

AU - Rochlin, Kate M.

AU - Wehrli, Marcel

AU - Schwartz, Stephanie L.

AU - DiNardo, Stephen

PY - 2006/5/1

Y1 - 2006/5/1

N2 - During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.

AB - During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.

KW - Arrow

KW - Endocytic trafficking

KW - Frizzled-2

KW - Wingless

UR - http://www.scopus.com/inward/record.url?scp=33646047425&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646047425&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2006.02.006

DO - 10.1016/j.ydbio.2006.02.006

M3 - Article

VL - 293

SP - 268

EP - 283

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 1

ER -