Abstract
The postsynaptic density or PSD is a submembranous compartment containing a wide array of proteins that contribute to both morphology and function of excitatory glutamatergic synapses. In this study, we have analyzed functional aspects of the Fezzin ProSAP-interacting protein 1 (ProSAPiP1), an interaction partner of the well-known PSD proteins Shank3 and SPAR. Using lentiviral-mediated overexpression and knockdown of ProSAPiP1, we found that this protein is dispensable for the formation of both pre- and postsynaptic specializations per se. We further show that ProSAPiP1 regulates SPAR levels at the PSD and the maturation of dendritic spines. In line with previous findings on the ProSAPiP1 homolog PSD-Zip70, we conclude that Fezzins essentially contribute to the maturation of excitatory spine synapses.
Highlights
The submembranous compartment of excitatory postsynapses contains a large amount of different proteins each contributing to the integrity of the so-called postsynaptic density (PSD; Boeckers, 2006)
This study was aimed at unraveling functional aspects of the Fezzin family member ProSAPiP1, a postsynaptic protein we originally identified as binding partner of both Shank3 and Spine-associated Rap GTPaseactivating proteins (SPARs) (Wendholt et al, 2006)
After viral infection of primary hippocampal neurons with an appropriate expression construct, we found that Green Fluorescent Protein (GFP)-ProSAPiP1 accumulates predominantly at excitatory synapses at later, mature stages of neuronal development in culture
Summary
The submembranous compartment of excitatory postsynapses contains a large amount of different proteins each contributing to the integrity of the so-called postsynaptic density (PSD; Boeckers, 2006). The Fezzins comprise four family members, ProSAPiP1, LAPSER1, PSD-Zip and N4BP3 that all share a Cterminal Fez domain They further exhibit coiled-coil domains mediating homo- and heteromultimerization among family members and bind to Spine-associated Rap GTPaseactivating proteins (SPARs), essential modulators of spine morphology. A study from 2007 further describes an ASD patient with the clinical diagnosis of Asperger’s syndrome and a spontaneous 1.1-Mb deletion of 20p13 encompassing the human ProSAPiP1 gene among others (Sebat et al, 2007) Based on these potentially disease-relevant findings on the Fezzin family and the complete lack of substantial data on the synaptic function of ProSAPiP1, we aimed to analyze this protein in primary hippocampal neurons in more detail. Via ProSAPiP1 overexpression and shRNAmediated ProSAPiP1 knock-down we show that this molecule is dispensable for the formation of pre- and post synaptic specializations per se, but provide evidence that it is involved in the regulation of SPAR levels at the PSD and the maturation of dendritic spines
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