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APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex

Cheryl A Nechamen1, Richard M Thomas, James A Dias

  • 1Wadsworth Center, David Axelrod Institute for Public Health, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, United States.

Molecular and Cellular Endocrinology
|October 13, 2006
PubMed

Insights

Follicle stimulating hormone receptor (FSHR) interacts with new proteins, APPL2 and FOXO1a. These interactions, along with APPL1 and Akt2, form distinct signaling networks that regulate FSH signal transduction.

Area of Science:

  • Molecular Cell Biology
  • Endocrinology
  • Signal Transduction

Background:

  • Follicle stimulating hormone receptor (FSHR) signaling is crucial for reproductive functions.
  • Several proteins, including APPL1, 14-3-3tau, and Akt2, are known to interact with FSHR.
  • The complete network of proteins involved in FSH-induced signal transduction remains incompletely defined.

Purpose of the Study:

  • To identify novel signaling and adapter proteins that associate with FSHR.
  • To elucidate the specific interactions between FSHR and identified proteins.
  • To understand the functional differences and network organization of these interacting proteins.

Main Methods:

  • Co-immunoprecipitation assays were used to examine protein-protein interactions.
  • Western blotting was employed to detect protein presence and interactions.
  • Analysis of protein sequence similarity and functional association with Akt2.

Main Results:

  • FSHR was found to interact with APPL2 and FOXO1a, in addition to the known interaction with APPL1.
  • APPL1 and APPL2 interact with each other via the N-terminus of APPL1, specifically through the Bin-Amphiphysin-Rvs (BAR) domain.
  • Distinct interaction patterns were observed: FOXO1a does not associate with APPL1 or APPL2, and APPL1 associates with Akt2 while APPL2 does not.
  • These findings reveal the first documented functional difference between APPL1 and APPL2.

Conclusions:

  • FSHR, APPL1, APPL2, Akt2, and FOXO1a form distinct scaffolding networks within the cell.
  • The spatial organization of these proteins with FSHR is critical for facilitating and regulating FSH-induced signal transduction.
  • This study expands our understanding of the molecular machinery governing FSH receptor signaling.

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