SYNAPTOPODIN - AN ACTIN-ASSOCIATED PROTEIN IN TELENCEPHALIC DENDRITESAND RENAL PODOCYTES

Synaptopodin is an actin-associated protein of differentiated podocyte s that also occurs as part of the actin cytoskeleton of postsynaptic d ensities (PSD) and associated dendritic spines in a subpopulation of e xclusively telencephalic synapses. Amino acid sequences determined in purified rat kidney and forebrain synaptopodin and derived from human and mouse brain cDNA clones show no significant homology to any known protein. In particular, synaptopodin does not contain functional domai ns found in receptor-clustering PSD proteins. The open reading frame o f synaptopodin encodes a polypeptide with a calculated M-r of 73.7 kD (human)/74.0 kD (mouse) and an isoelectric point of 9.38 (human)/9.27 (mouse). Synaptopodin contains a high amount of proline (similar to 20 %) equally distributed along the protein, thus virtually excluding the formation of any globular domain. Sequence comparison between human a nd mouse synaptopodin revealed 84% identity at the protein level. In b oth brain and kidney, in vivo and in vitro, synaptopodin gene expressi on is differentiation dependent. During postnatal maturation of rat br ain, synaptopodin is first detected by Western blot analysis at day 15 and reaches maximum expression in the adult animal. The exclusive syn aptopodin synthesis in the telencephalon has been confirmed by in situ hybridization, where synaptopodin mRNA is only found in perikarya of the olfactory bulb, cerebral cortex, striatum, and hippocampus, i.e., the expression is restricted to areas of high synaptic plasticity. Fro m these results and experiments with cultured cells we conclude that s ynaptopodin represents a novel kind of proline-rich, actin-associated protein that may play a role in modulating actin-based shape and motil ity of dendritic spines and podocyte foot processes.