Regulation of bifunctional proteins in cells: Lessons from the phospholipase Cβ/G protein pathway

Abstract

Some proteins can serve multiple functions depending on different cellularconditions. An example of a bifunctional protein is inositide-specific mammalian phospholipase Cβ (PLCβ). PLCβ is activated by G proteins in response to hormones and neurotransmitters to increase intracellular calcium. Recently, alternate cellular function(s) of PLCβ have become uncovered. However, the conditions that allow these different functions to be operative are unclear. Like many mammalian proteins, PLCβ has a conserved catalytic core along with several regulatory domains. These domains modulate the intensity and duration of calcium signals in response to external sensory information, and allow this enzyme to inhibit protein translation in a noncatalytic manner. In this review, we first describe PLCβ's cellular functions and regulation of the switching between these functions, and then discuss the thermodynamic considerations that offer insight into how cells manage multiple and competitive associations allowing them to rapidly shift between functional states.

Phosphatidylinositol 4,5‐bisphosphate‐specific phospholipase C β1 selectively binds dipalmitoyl and distearoyl phosphatidic acids via Lys946 and Lys951

“…To assess the physiological roles of Lys946 and Lys951, we expressed AcGFP‐tagged PLCβ1 (WT) and PLCβ1‐KE in Neuro‐2a cells. PLCβ1 was primarily located at the plasma membrane (Figure 6a, c), as reported previously (Jackson et al, 2020). However, PLCβ1‐KE was located in the cytoplasm (Figure 6a, c).…”

Activation of Gαq sequesters specific transcripts into Ago2 particles

“…The basis of this pathway stems from the multifunctional nature of PLCβ1. PLCβ1 has several conserved structural domains surrounding the catalytic domain along with a long 400aa tail that is required for Gαq binding, and that can mediate binding to cytosolic partners (see 23 ). One of these confirmed partners is the Promoter of RNA-induced silencing, C3PO 24 , 25 , which is inhibited by PLCβ1 binding 3 , 26 – 28 .…”

Neurotransmitter Activation Sequesters Specific mRNAs Into Stress Granules

“…The basis of this pathway stems from the multifunctional nature of PLCβ1. PLCβ1 has several conserved structural domains surrounding the catalytic domain along with a long 400aa tail that is required for Gαq binding, and that can mediate binding to cytosolic partners (see [24]). One of these con rmed partners is the Promoter of RNA-induced silencing, C3PO [25,26], which is inhibited by PLCβ1 binding [3,[27][28][29].…”