Exclusive or promiscuous? Role(s) of the moonlighting auxiliary subunit PORCN in AMPA receptor physiology

点击翻译按钮获取中文摘要

AMPA-type glutamate receptors (AMPARs) are the major excitatory neurotransmitter receptors in the mammalian central nervous system. AMPAR complexes assemble as heterotetramers of the four ion channel pore-forming subunits GluA1-4 and a variety of auxiliary subunits that modulate receptor trafficking and gating. In addition to the well-studied transmembrane AMPA receptor regulatory proteins (TARPs) and cornichons (CNIH-2/3), recent mass spectrometric analyses revealed a surprisingly high number of additional AMPAR-associated proteins. Understanding how this large and diverse protein collection modulates AMPARs is an important challenge.One of the newly discovered AMPAR-interacting proteins is the palmitoyl transferase porcupine (PORCN). First experimental evidence indicates that PORCN can stabilize neuronal AMPAR complexes and thereby enhances glutamatergic synaptic transmission. Besides its moonlighting role in AMPAR signaling, it has been reported that PORCN serves a canonical function in Wnt signaling.Here, we intend to apply a multi-disciplinary approach combining cell-biological, biochemical and electrophysiological techniques in order to investigate the role of PORCN in AMPAR physiology in more detail. In addition, we will unravel the molecular mechanisms that regulate PORCN´s multi-functionality and thereby significantly increase our understanding of moonlighting proteins.