Polycystin-1 can interact with homer 1/Vesl-1 in postnatal hippocampal neurons

• Published in: Journal of neuroscience research 2006-12, Vol.84 (8), p.1727-1737
• Main Authors: Stokely, Martha E., Hwang, Sung-Yong, Hwang, Ji-yeon, Fan, Betty, King, Michael A., Inokuchi, Kaoru, Koulen, Peter
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Blotting, Western - methods; calcium signaling; Carrier Proteins - metabolism; Cells, Cultured; hippocampus; Hippocampus - cytology; homer 1a/Vesl-1S; Homer Scaffolding Proteins; Immunohistochemistry - methods; Immunoprecipitation - methods; Mice; Mice, Inbred C57BL; Models, Biological; Neurofilament Proteins - metabolism; Neurons - metabolism; remodeling; synaptic plasticity; TRPP Cation Channels - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21076

Polycystin‐1 (PC‐1) has been identified as critical to development of the nervous system, but the significance of PC‐1 expression in neurons remains undefined, and little is known of its roles outside the kidney, where mutation results in autosomal dominant polycystic kidney disease (ADPKD). In kidney, PC‐1 interacts with cadherins, catenins, and its cognate calcium channel polycystin‐2 (PC‐2), which in turn interacts with a number of actin‐regulatory proteins. Because some of the proteins that interact with PC‐1 in kidney also participate in synaptic remodeling and plasticity in the hippocampus, we decided to test PC‐1's potential to interact with a recently discovered type of plasticity‐associated protein (homer 1a/Vesl‐1S) in postnatal mouse hippocampus. Homer 1a/Vesl‐1S is an activity‐induced protein believed to participate in synaptic remodeling/plasticity responses to temporal lobe seizure and learning. Here we report the following. 1) PC‐1 contains a homer‐binding motif (PPxxF), which lies within its purported cytoplasmic domain. 2) Immunoreactivity for PC‐1 (PC‐1‐ir) is highly colocalized with homer 1a immunoreactivity (H1a‐ir) in primary cultured hippocampal neurons. 3) PC‐1‐ir and H1a‐ir are present and appear to be colocalized in mouse hippocampus but not cortex on postnatal day 2 (P2), when higher frequencies of spontaneous activity are normal for hippocampus compared with cortex. 4) An endogenous PC‐1‐ir band with the correct size for the reported C‐terminal G‐protein‐sensitive domain cleavage product of PC‐1 (∼150 kDa) coimmunoprecipitates with endogenous homer 1/Vesl‐1 proteins from mouse brain, suggesting that PC‐1 can interact with homer 1/Vesl‐1 proteins in postnatal hippocampal neurons. © 2006 Wiley‐Liss, Inc.