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Identifying Protein-protein Interaction in Drosophila Adult Heads by Tandem Affinity Purification (TAP)

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Critical role for TARPs in early development despite broad functional redundancy.

Karen Menuz¹, Geoffrey A Kerchner, Jessica L O'Brien

¹Department of Cellular and Molecular Pharmacology, University of California, Campus Box 2140, 600 16th Street, San Francisco, CA 94143-2140, USA.

Neuropharmacology

|July 19, 2008

Summary

Transmembrane AMPA receptor regulatory proteins (TARPs) are essential for early development. Loss of multiple TARPs, especially gamma-2, leads to non-viable mice, highlighting their critical role in neuronal function.

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Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits crucial for AMPA receptor function.
Previous studies suggested TARPs associate with nearly all native AMPA receptors.

Purpose of the Study:

To investigate the in vivo interplay between TARP family members and AMPA receptors.
To determine the necessity of specific TARP combinations for survival and neuronal function.

Main Methods:

Generation and analysis of triple knockout mice lacking combinations of TARP family members (gamma-2, gamma-3, gamma-4, gamma-8).
Assessment of mouse viability, fertility, and AMPA receptor function in cortical and spinal neurons.

Main Results:

Triple knockout mice lacking gamma-3, gamma-4, and gamma-8 were viable with reduced synaptic AMPA receptor activity.
Triple knockout mice lacking gamma-2, gamma-3, and either gamma-4 or gamma-8 were not viable, exhibiting apnea and paralysis.
Early expression of gamma-8 was found to regulate AMPA receptor levels during early development.

Conclusions:

TARPs, particularly gamma-2, are essential for early mammalian development.
Most neurons express multiple, functionally redundant TARP family members.
Early gamma-8 expression is critical for maintaining neonatal neuronal AMPA receptor function.