PKC zeta-interacting protein ZIP3 is generated by intronic polyadenylation, and is expressed in the brain and retina of the rat

Scaffold proteins contain multiple protein protein interaction modules that physically assemble functionally related proteins into larger complexes. ZIPs [PKC (protein kinase C) zeta-interacting proteins] link the enzymatic activity of the atypical PKC isoforms PKC lambda/iota or PKC zeta to target proteins and are associated with neurodegenerative disorders. In the rat, alternative splicing generates three ZIP variants. Previously, we identified the ZIP3 transcript, containing 13 C-terminal amino acids encoded by intron 4, in the rat CNS (central nervous system). In the present study, we identified intronic polyadenylation signals in rat and human ZIP genes [known as SQSTM1 (sequestosome-1) in humans] and detected the corresponding ZIP3-like transcripts. In addition, we generated ZIP3-specific immune sera and observed expression of the protein in the brain and retina of the adult rat. In the retina, ZIP3 is present in nuclear layers where it co-localizes with PKC zeta. An immune serum recognizing all three ZIP isoforms labelled the same cells as the newly generated ZIP3-specific antibodies and, in addition, stained both synaptic layers of the retina. There, ZIPs are localized in axon terminals of rod bipolar cells that also contain ZIP-interacting PKC zeta and GABA(C) (gamma-aminobutyric acid type C) receptors. In summary, we detected ZIP3-like transcripts in rat- and human-derived samples and describe the expression of ZIP3 in the rat CNS.