Ppp1ca-flox Mouse

Ppp1ca, encoding Protein phosphatase 1 catalytic subunit alpha, is a key component of the PP1 complex. It is involved in regulating diverse cellular processes such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription [7]. It participates in multiple pathways like the regulation of TFEB-dependent autophagy, glucose metabolism, and the AKT-mTOR signaling pathway, which are crucial for maintaining normal cellular functions and organismal health [1,2,3]. The generation of a PPP1CA knockout human pluripotent stem cell line using the CRISPR/Cas9 system provides a valuable research model for further exploring its functions [7].

In the context of diseases, in intervertebral disc degeneration, increased K141-methylation of PPP1CA disrupts its interaction with TFEB, blocking TFEB dephosphorylation and nuclear translocation, leading to autophagy deficiency and NPC senescence [1]. In osteoporosis, CARM1 methylates R23 of PPP1CA, affecting glucose metabolism-related phosphorylation events and ultimately influencing osteogenic and osteoclastic differentiation [2]. In clear cell renal cell carcinoma, a peptide encoded by circPDHK1 interacts with PPP1CA, inhibiting AKT dephosphorylation and activating the AKT-mTOR signaling pathway to promote cancer progression [3]. In diabetic retinopathy, PPP1CA activates retinal Müller cells through the PPP1CA/YAP/GS/Gln/mTORC1 pathway [4]. In colorectal cancer, circGPRC5A stabilizes PPP1CA protein, enhancing YAP dephosphorylation and promoting cancer progress [5]. In salt-sensitive hypertension, dietary potassium stimulates Ppp1Ca-Ppp1r1a-mediated dephosphorylation of the kidney NaCl cotransporter, reducing blood pressure [6]. In glioblastoma, KIF18A interacts with PPP1CA to promote the malignant development of the tumor [8].

In summary, Ppp1ca plays essential roles in multiple biological processes and is implicated in various disease conditions. The use of gene knockout models, such as the PPP1CA knockout human pluripotent stem cell line, has provided significant insights into its functions in different diseases, helping to understand the underlying mechanisms and potentially guiding the development of therapeutic strategies for these diseases.