Phospholipase D1 Signaling: Essential Roles in Neural Stem Cell Differentiation

Abstract

Phospholipase D1 (PLD1) is generally accepted as playing an important role in the regulation of multiple cell functions, such as cell growth, survival, differentiation, membrane trafficking, and cytoskeletal organization. Recent findings suggest that PLD1 also plays an important role in the regulation of neuronal differentiation of neuronal cells. Moreover, PLD1-mediated signaling molecules dynamically regulate the neuronal differentiation of neural stem cells (NSCs). Rho family GTPases and Ca2+-dependent signaling, in particular, are closely involved in PLD1-mediated neuronal differentiation of NSCs. Moreover, PLD1 has a significant effect on the neurogenesis of NSCs via the regulation of SHP-1/STAT3 activation. Therefore, PLD1 has now attracted significant attention as an essential neuronal signaling molecule in the nervous system. In the current review, we summarize recent findings on the regulation of PLD1 in neuronal differentiation and discuss the potential role of PLD1 in the neurogenesis of NSCs.

BCALM (AC099524.1) Is a Human B Lymphocyte–Specific Long Noncoding RNA That Modulates B Cell Receptor–Mediated Calcium Signaling

“…6 (27,28,31,32). PLD1 produces PA, which activates SHP-1 (26,97), a phosphatase that inhibits BCR-associated kinases and downregulates BCR signaling (71, 72, 75, 98, 99) (Fig. 6A).…”

“…Instead, BCALM is localized to the cytoplasm and interacts with phospholipase D 1 (PLD1) and A-kinase proteins AKAP9 (AKAP450) and AKAP13 (AKAP-Lbc). AKAPs assemble kinase signaling complexes to ensure correct subcellular targeting, including protein kinase A (PKA) and protein kinase C (PKC), which phosphorylate and activate PLD1 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30). PLD1 hydrolyzes lipid membrane component phosphatidylcholine to phosphatidic acid (PA), which activates the SHP-1 phosphatase (26,31,32), a negative regulator of BCR signaling (33,34).…”

“…AKAPs assemble kinase signaling complexes to ensure correct subcellular targeting, including protein kinase A (PKA) and protein kinase C (PKC), which phosphorylate and activate PLD1 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30). PLD1 hydrolyzes lipid membrane component phosphatidylcholine to phosphatidic acid (PA), which activates the SHP-1 phosphatase (26,31,32), a negative regulator of BCR signaling (33,34). KO of AC099524.1 (BCALM) abrogated the association of PLD1 and AKAP9, attenuated phosphorylation of PLD1 and enhanced calcium flux after BCR stimulation.…”

mRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell

“…At the same time, in addition to the fact that some DEGs were VTGs or PTGs of miR-31-5p, there were interaction networks between DEGs and some VTGs of miR-31. Among them, Stat3 was an important transcription factor regulating the expression of Gfap 44 ; Sod2 played an important role in the regulation of cell cycle 45 ; and Gsk3b could be used as a signal "node" to coordinate multiple key signaling pathways in NSCs 46,47 . Based on the above analysis, we conclude that the action mechanism of miR-31 in early stage of NSCs after overexpression was not showed that in addition to the general function prediction only of COG classification, no matter the up or down regulated DEmiRNAs, distribution of PTGs were mostly in transcription, replication, recombination and repair, signal transduction mechanisms.…”

“…At the same time, in addition to the fact that some DEGs were VTGs or PTGs of miR-31-5p, there were interaction networks between DEGs and some VTGs of miR-31. Among them, Stat3 was an important transcription factor regulating the expression of Gfap 44 ; Sod2 played an important role in the regulation of cell cycle 45 ; and Gsk3b could be used as a signal "node" to coordinate multiple key signaling pathways in NSCs 46 , 47 . Based on the above analysis, we conclude that the action mechanism of miR-31 in early stage of NSCs after overexpression was not only to inhibit its target gene, but also to expand its action scope by regulating the expression of other miRNAs, ultimately increasing the expression of genes or miRNAs related to NSCs stemness maintenance, and inhibiting NSCs, especially MNs, differentiation-related genes, through protein interaction and DEmiRNAs, to maintain the undifferentiated state of NSCs.…”