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. Author manuscript; available in PMC: 2020 Feb 1.
Published in final edited form as: Steroids. 2018 Jan 31;142:77–83. doi: 10.1016/j.steroids.2018.01.010

Figure 1.

Figure 1

A model cell illustrating the Gq-mER signaling pathway in hypothalamic neurons. (1) E2 (or STX) activates a membrane-associated ER (mER) that is Gq-coupled. The Gαq protein activates PLC to catalyze the hydrolysis of membrane-bound PIP2 into IP3 and DAG. (2) DAG activates PKCδ to augment adenylyl cyclase (ACVII) activity and generate cAMP, which in turn activates PKA. (3) In POMC neurons, activation of PKA attenuates the GABA-B receptor-mediated activation of GIRK channels, while in NPY neurons, PKA activation potentiates GIRK channel activity. (4) In CRH neurons, PKA phosphorylates KCNQ subunits to inhibit the M-current, which may also be inhibited by the hydrolysis of PIP2 in the membrane into free IP3 and DAG. (5) PKA activation may also lead to the phosphorylation of AMPAR subunits augmenting membrane trafficking and recruitment to rapidly increase the amplitude of AMPAR currents in CRH neurons. (6) STX also increases the expression of Cav3 (T-type Ca2+) channels in GnRH neurons, presumably through the PKA-mediated phosphorylation of pCREB, leading to gene regulation through the cAMP response element (CRE). (7) Activation of the Gq-mER has also been associated with PI3K and ERK signaling pathways in hypothalamic and hippocampal neurons.