Table 1.

Brief summary of activity-dependent nucleocytoplasmic shuttling of CRTC1 and its role in synaptic plasticity and memory.

References	System	Findings
(Zhou et al., 2006)	Cultured hippocampal neurons Hippocampal slices	Neuronal stimulation induces nuclear translocation of CRTC1.
		CRTC1 regulates neuronal stimulation-induced gene expression of Bdnf.
		TORC1 nuclear translocation correlates with late-phase LTP induction.
		Requirement of TORC1 for late-phase LTP.
(Kovacs et al., 2007)	Cultured hippocampal or cortical neurons Hippocampal slice cultures	CRTC1 imports to the nucleus upon activation of calcium and cAMP pathways.
		CRTC1 mediates the synergistic activation of CREB-mediated transcription by calcium and cAMP in neurons.
		CRTC1 is involved in L-LTP maintenance in the Schaffer collateral–CA1 pathway.
(Li et al., 2009)	Cultured cortical neurons	Increased nuclear translocation of CRTC1 in response to neuronal stimulation.
		CRTC1 is required for activity-induced dendrite arborization.
	Mouse	CRTC1 is required for dendrite growth in the cortex.
(Espana et al., 2010)	Cultured hippocampal neurons	Amyloid β oligomers impair CRTC1-dependent signaling. impair
		Amyloid β impairs CRTC1/CREB-dependent transcription by CRTC1/CREB affecting CRTC1 dephosphorylation.
	Mouse	Gene transcription mediated by CRTC1 is impaired in the hippocampus from an animal model of Alzheimer’s disease.
(Ch'ng et al., 2012)	Cultured hippocampal neurons	Activity-dependent synapse-to-nucleus translocation of CRTC1 in excitatory neurons.
		Nuclear translocation of CRTC1 requires activation of calcineurin. cAMP regulates the persistence of CRTC1 in the nucleus.
		CRTC1 is required for activity-dependent induction of specific CREB target genes (c-fos, Arc, Zif268).
	Hippocampal slice cultures	Chemical LTP induces synapse-to-nucleus translocation of CRTC1.
(Sekeres et al., 2012)	Mouse	Herpes simplex virus-mediated local and acute increase of CRTC1 levels in the dentate gyrus of hippocampus during training enhances consolidation of contextual fear memory.
		Increasing CRTC1 levels in the dentate gyrus of hippocampus enhances reconsolidation of an established contextual fear memory.
(Parra-Damas et al., 2014)	Mouse	Learning (Morris water maze)-induces nuclear accumulation of CRTC1 in the CA1 and CA3 subregion of hippocampus.
	Human	Altered CRTC1 levels and transcriptional changes (ARC, NR4A2) in human brain at intermediate Alzheimer's disease pathological stages.
(Nonaka et al., 2014)	Cultured hippocampal or cortical neurons	Dephosphorylation of CRTC1 at Ser151 and Ser245 is critical for its activity-dependent nuclear import and CRE-dependent transcriptional activity.
		CRTC1 mutant lacking calcineurin-binding motifs disrupts nuclear translocation of CRTC1 following neuronal stimulation.
	Mouse	Overexpression of the constitutive active form of CRTC1 (Ser151Ala/Ser245/Ala) in the CA suregion of hippocampus enhances activity-dependent gene expression (Arc, c-fos, Bdnf) and long-term fear memory formation.
		Learning (contextual fear conditioning) induces nuclear accumulation of CRTC1 in the basolateral amygdala.
		Knockdown of CRTC1 in the basolateral amygdala reduces long-term fear memory.
		Overexpression of the constitutive active form of CRTC1 induces a significant enlargement of spine heads.
(Uchida et al., 2017)	Primary hippocampal neurons	Neuronal stimulation induces nuclear translocation of CRTC1.
		Two phosphorylation sites of CRTC1 at Ser151 and Ser167 are important for its nuclear retention rather than nuclear import following neuronal stimulation.
	Mouse	Learning (contextual fear conditioning and object location task) induces synapse-to nucleus translocation of CRTC1 in the CA subregion of hippocampus and these are dependent on the strength of learning.
		Learning-induced nuclear translocation of CRTC1 is dependent on microtubule stability.
		Loss-of-function CRTC1 in the CA subregion of hippocampus disrupts LTP and long-term memory.
		Gain-of-function CRTC1 in the CA subregion of hippocampus leads to memory enhancement.
		Calcineurin-mediated CRTC1 nuclear translocation is required for memory enhancement.
		CRTC1/CREB/KAT5-mediated epigenetic regulation of Fgf1b expression is required for memory enhancement.
(Parra-Damas et al., 2017)	Mouse	Contextual fear learning induces CRTC1 dephosphorylation in the hippocampus.
		Contextual fear learning induces CRTC1 nuclear translocation in the CA3 subregion of hippocampus.

Please note that the findings listed here do not cover all the contents of the reference papers and that we do not cite all the related articles here, due to the space limitation,