ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the postsynaptic density that links the spine-associated Rap-Gap (SPAR) to the scaffolding protein ProSAP2/Shank3.
ProSAPs/Shanks are a family of proteins that have a major scaffolding function for components of the postsynaptic density (PSD) of excitatory brain synapses. Members of the family harbor a variety of domains for protein-protein interactions, one of which is a unique PDZ domain that differs significantly from those of other proteins. We have identified a novel binding partner for this PDZ domain, termed ProSAPiP1, that is highly enriched in the PSD and shares significant sequence homology with the PSD protein PSD-Zip70. Both molecules code for a Fez1 domain that can be found in a total of four related proteins. ProSAPiP1 is widely expressed in rat brain and co-localizes with ProSAP2/Shank3 in excitatory spines and synapses. ProSAP2/Shank3 co-immunoprecipitates with ProSAPiP1 but not with PSD-Zip70. Both proteins, however, bind and recruit SPAR to synapses with a central coiled-coil region that harbors a leucine zipper motif. This region is also responsible for homo- and heteromultimerization of ProSAPiP1 and PSD-Zip70. Thus, ProSAPiP1 and PSD-Zip70 are founders of a novel family of scaffolding proteins, the "Fezzins," which adds further complexity to the organization of the PSD protein network.
Wendholt
Doreen
D
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Spilker
Christina
C
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Schmitt
Angelika
A
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Dolnik
Anna
A
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Smalla
Karl-Heinz
KH
AG Molecular Mechanisms of Plasticity, Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Proepper
Christian
C
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Bockmann
Juergen
J
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Sobue
Kenji
K
Department of Neuroscience, Osaka University School of Medicine, Suita, Osaka 565, Japan.
Gundelfinger
Eckart D
ED
AG Molecular Mechanisms of Plasticity, Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Kreutz
Michael R
MR
AG Molecular Mechanisms of Plasticity, Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany,. Electronic address: michael.kreutz@ifn-magdeburg.de.
Boeckers
Tobias M
TM
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany. Electronic address: tobias.boeckers@uni-ulm.de.
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats
D048868:Adaptor Proteins, Signal Transducing; D020690:GTPase-Activating Proteins; C475881:Lzts1 protein, rat; D009419:Nerve Tissue Proteins; C120532:Shank3 protein, rat; C479629:Sipa1l1 protein, rat