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PMID: 22791894 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Type II phosphatidylinositol 4-kinase regulates trafficking of secretory granule proteins in Drosophila.

Development (Cambridge, England) ·Vol. 139 ·No. 16 ·2012-08-00 ·Pages 3040-50

Burgess J, Del Bel LM, Ma CI, Barylko B, Polevoy G, Rollins J, Albanesi JP, Krämer H, Brill JA

Abstract

Type II phosphatidylinositol 4-kinase (PI4KII) produces the lipid phosphatidylinositol 4-phosphate (PI4P), a key regulator of membrane trafficking. Here, we generated genetic models of the sole Drosophila melanogaster PI4KII gene. A specific requirement for PI4KII emerged in larval salivary glands. In PI4KII mutants, mucin-containing glue granules failed to reach normal size, with glue protein aberrantly accumulating in enlarged Rab7-positive late endosomes. Presence of PI4KII at the Golgi and on dynamic tubular endosomes indicated two distinct foci for its function. First, consistent with the established role of PI4P in the Golgi, PI4KII is required for sorting of glue granule cargo and the granule-associated SNARE Snap24. Second, PI4KII also has an unforeseen function in late endosomes, where it is required for normal retromer dynamics and for formation of tubular endosomes that are likely to be involved in retrieving Snap24 and Lysosomal enzyme receptor protein (Lerp) from late endosomes to the trans-Golgi network. Our genetic analysis of PI4KII in flies thus reveals a novel role for PI4KII in regulating the fidelity of granule protein trafficking in secretory tissues.

MeSH Terms
1-Phosphatidylinositol 4-Kinase/genetics,metabolism Animals Animals, Genetically Modified Drosophila Proteins/genetics,metabolism Drosophila melanogaster/genetics,growth & development,metabolism Endosomes/metabolism Glue Proteins, Drosophila/metabolism Golgi Apparatus/metabolism Luminescent Proteins/genetics,metabolism Models, Biological Protein Transport Salivary Glands/growth & development,metabolism Secretory Vesicles/metabolism rab GTP-Binding Proteins/genetics,metabolism rab7 GTP-Binding Proteins
Chemicals
Drosophila Proteins Glue Proteins, Drosophila Luminescent Proteins rab7 GTP-Binding Proteins 1-Phosphatidylinositol 4-Kinase rab GTP-Binding Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Burgess Jason
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 1L7, Canada.
Del Bel Lauren M
Ma Cheng-I J
Barylko Barbara
Polevoy Gordon
Rollins Janet
Albanesi Joseph P
Krämer Helmut
Brill Julie A
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
1477-9129
DOI
10.1242/dev.077644
Published
2012-08-00
Epub
2012-00-12
Pages
3040-50
Language
English
Region
England
NLM ID
8701744
PMCID
PMC3403109
Subset
IM
Grants
NEI NIH HHS · R01 EY010199 · United States
CIHR · MOP-119483 · Canada
CIHR · IG1-115714 · Canada
CIHR · TGF-53877 · Canada
NIGMS NIH HHS · GM075401 · United States
NIGMS NIH HHS · R01 GM075401 · United States
NEI NIH HHS · EY10199 · United States
External Links
PubMed source DOI: 10.1242/dev.077644 PMC Full Text View journal details
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