Table 1. Externally validated CA2-enriched proteins.

Here, we list expression (mRNA and protein) and known function of proteins that we found to have robustly enriched expression in CA2 (vs. CA1). These 18 proteins have been previously shown in the literature to be enriched in CA2 through examination of mRNA and/or protein expression and provide external validation of the methods used to isolate and analyze areas CA1 and CA2 for this study.

Gene Symbol	Protein name	Validation by mRNA	Validation by Protein	Known Function in neurons
DGKG	Diacylglycerol kinase gamma	Yes71	N/A	N/A
MCU	Mitochondrial Calcium Uniporter	Yes71	N/A	Main component of the protein complex that mediates mitochondrial calcium uptake56
NECAB2	N-terminal EF-hand calcium-binding protein 2	Yes45	Yes45	Interacts with and modulates the activity of the adenosine 2A receptor72 and metabotropic glutamate receptor 573
ACTN2	Alpha-actinin 2	N/A	Yes11, 42	Mediates spine morphology and assembly of the post-synaptic density in hippocampal neurons,52 anchoring PSD-95 at post-synaptic sites53
SMS	Spermine synthase	Yes71	N/A	Converts spermidine to spermine, a polyamine which has multiple effects54 including modulation of NMDA receptor function55
PRKCE	Protein kinase C ε	N/A	Yes74	Activation and increased expression of this kinase mediates neuroprotection following oxygen and glucose deprivation62
SLC25A22	Mitochondrial glutamate carrier 1	Yes71	N/A	Transports glutamate into the inner mitochondrial membrane75
RGS14	Regulator of G protein signaling 14	Yes71	Yes6–8	Natural suppressor of LTP in the CA2 region of the hippocampus6 through modulation of calcium signaling43· 44
OSTF1	Osteoclast-stimulating factor 1	Yes71	Yes76	N/A
CADPS	Calcium-dependent secretion activator 1	Yes71	N/A	Essential factor for synaptic vesicle priming in hippocampal neurons60
GPC1	Glypican-1	Yes71	N/A	N/A
PPFIA2	Liprin-alpha 2	No77	Yes78	Controls synaptic output by regulating synaptic vesicle pool size59
KCTD4	Potassium channel tetramerization domain containing 4	Yes71	N/A	N/A
RYR2	Ryanodine receptor 2	No71	Yes79· 80	Mediates calcium-induced calcium release from intracellular calcium stores57, affecting cognitive function and hippocampal synaptic plasticity in chronically stressed mice81
ATP8A1	ATPase phospholipid transporting 8A1	Yes71	N/A	Deficiency in this flippase is associated with externalization of phosphatidylserine in hippocampal neurons, delaying hippocampal-dependent learning63
NRP1	Neuropilin 1	Yes71	N/A	Interacts with semaphoring 3 and VEGF to mediate axon guidance and angiogenesis respectively58
ANXA11	Annexin A11	Yes71	N/A	Participates in ER-to-Golgi trafficking, modulating the early secretory pathway82
CLVS2	Clavesin 2	Yes71	N/A	Regulates late endosome/lysosome morphology83