Conservation and expression of IQ‐domain‐containing calpacitin gene products (neuromodulin/GAP‐43, neurogranin/RC3) in the adult and developing oscine song control system

Abstract

Songbirds are appreciated for the insights they provide into regulated neural plasticity. Here we describe the comparative analysis and brain expression of two gene sequences encoding probable regulators of synaptic plasticity in songbirds: Neuromodulin (GAP-43) and Neurogranin (RC3). Both are members of the calpacitin family and share a distinctive conserved core domain that mediates interactions between calcium, calmodulin and protein kinase C signaling pathways. Comparative sequence analysis is consistent with known phylogenetic relationships, with songbirds most closely related to chicken and progressively more distant from mammals and fish. The C-terminus of Neurogranin is different in birds and mammals, and antibodies to the protein reveal high expression in adult zebra finches in cerebellar Purkinje cells, which has not been observed in other species. RNAs for both proteins are generally abundant in the telencephalon yet markedly reduced in certain nuclei of the song control system in adult canaries and zebra finches: Neuromodulin RNA is very low in RA and HVC (relative to the surrounding pallial areas), whereas Neurogranin RNA is conspicuously low in Area X (relative to surrounding striatum). In both cases, this selective down-regulation develops in the zebra finch during the juvenile song learning period, 25–45 days after hatching. These results suggest molecular parallels to the robust stability of the adult avian song control circuit.

Structural Basis for the Interaction of Unstructured Neuron Specific Substrates Neuromodulin and Neurogranin with Calmodulin

“…Therefore, Nm and Ng might serve as a Ca 2+ -regulated modulators of CaM activity in neurons. Moreover, the strict conservation of the region containing the IQ motif in all vertebrates suggests that both the PKC phosphorylation site and the CaM binding feature are essential to the functions of Nm and Ng3. Although the functions of Nm and Ng have been well established, the intrinsically unstructured nature of these two proteins, and the consequential lack of structural information, has seriously hampered a complete understanding of the interaction between Nm/Ng and CaM.…”

“…Neuromodulin (Nm) and neurogranin (Ng) are neuron-specific substrate proteins belonging to the calpacitin protein family123. Nm and Ng share high sequence similarity spanning a 20-amino-acid region that contains an IQ motif (I/L/V)QXXXRXXXX(R/K).…”

Frank Beach Award Winner: Steroids as neuromodulators of brain circuits and behavior

“…In a similar vein, there are three apparently independently evolved clades of vocal learning in birds (parrots, hummingbirds, and oscine songbirds), which offer a rich diversity of neural networks that are similar but not identical in their connectivity. Although there has been a good deal of exploration into the neural, neurogenetic and hormonal similarities among these three clades of avian vocal learners (Clayton et al, 2009; Hara et al, 2012; Jarvis et al, 2013; Replogle et al, 2008), it also remains to be tested whether networks of neurons involved in song learning are similarly regulated by the actions of neuromodulators to support a complex behavior that has evolved independently.…”

Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

“…In the adult zebra finch, Ng expression is high in most telencephalic areas except in the song areas, where expression is very low. However, during the juvenile period, Ng expression in these areas is high but diminishes dramatically when the song learning period finishes (101). This finding suggests that Ng expression is important for the learning process, and also, that a drastically reduced Ng expression is necessary to stabilize synapses and circuits responsible for the invariant reproduction of the singing.…”