The Drosophila F-box protein Fbxl7 binds to the protocadherin Fat and regulates Dachs localization and Hippo signaling

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Abstract

The Drosophila protocadherin, Fat (Ft) regulates growth, planar cell polarity (PCP) and proximodistal patterning. A key downstream component of Ft signaling is the atypical myosin Dachs (D). Multiple regions of the intracellular domain of Ft have been implicated in regulating growth and PCP but how Ft regulates D is not known. Mutations in Fbxl7, which encodes an F-box protein, result in tissue overgrowth and abnormalities in proximodistal patterning that phenocopy deleting a specific portion of the intracellular domain (ICD) of Ft that regulates both growth and PCP. Fbxl7 binds to this same portion of the Ft ICD, co-localizes with Ft to the proximal edge of cells and regulates the levels and asymmetry of D at the apical membrane. Fbxl7 can also regulate the trafficking of proteins between the apical membrane and intracellular vesicles. Thus Fbxl7 functions in a subset of pathways downstream of Ft and links Ft to D localization.

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Justin A Bosch

University of California, Berkeley, Berkeley, United States

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The authors declare that no competing interests exist.
Taryn M Sumabat

University of California, Berkeley, Berkeley, United States

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The authors declare that no competing interests exist.
Yassi Hafezi

University of California, Berkeley, Berkeley, United States

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The authors declare that no competing interests exist.
Brett J M Pellock

Providence College, Providence, United States

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The authors declare that no competing interests exist.
Kevin D Gandhi

University of California, Berkeley, Berkeley, United States

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The authors declare that no competing interests exist.
Iswar K Hariharan

University of California, Berkeley, Berkeley, United States

For correspondence
ikh@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: Custom antibodies used in this study were generated in guinea pigs by the vendor Pocono Rabbit Farm and Laboratory. Pocono Rabbit Farm and Laboratory, Inc. has an Animal Welfare Assurance on file with The Office of Laboratory Animal Welfare (OLAW). The Animal Welfare Assurance number is A3886-01. This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

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