Mining recent brain proteomic databases for ion channel phosphosite nuggets

Abstract

Voltage-gated ion channels underlie electrical activity of neurons and are dynamically regulated by diverse cell signaling pathways that alter their phosphorylation state. Recent global mass spectrometric-based analyses of the mouse brain phosphoproteome have yielded a treasure trove of new data as to the extent and nature of phosphorylation of numerous ion channel principal or α subunits in mammalian brain. Here we compile and review data on 347 phosphorylation sites (261 unique) on 42 different voltage-gated ion channel α subunits that were identified in these recent studies. Researchers in the ion channel field can now begin to explore the role of these novel in vivo phosphorylation sites in the dynamic regulation of the localization, activity, and expression of brain ion channels through multisite phosphorylation of their principal subunits.

Figure 1.

Schematic of phosphosites identified in high-throughput studies on 24 transmembrane segment ion channel α subunits. Areas of the green circles represent the percentage of phosphosites found within a specific cytoplasmic domain (N-terminal, ID I-II, ID-II-III, or C-terminal). Numbers adjacent to circles represent the total number of unique phosphosites identified within that domain for all members of that family (Cav: six members; Nav: four members).

Figure 2.

Schematic of phosphosites identified in high-throughput studies on six transmembrane segment ion channel α subunits. Areas of the green circles represent the percentage of phosphosites found within a specific cytoplasmic domain (N or C terminus). Numbers adjacent to circles represent the total number of unique phosphosites identified within that domain for all members of that family (Kv1-4: 14 members; Kv7: 3 members; Kv10: 4 members; Slo1-BK: 1 member; HCN: 4 members; TRP: 5 members).