Association of the ecto‐ATPase NTPDase2 with glial cells of the peripheral nervous system

Abstract

Cellular signaling via extracellular nucleotides appears to play a major role in the functioning of the peripheral nervous system. Information regarding the functional characterization of nucleotide P2 receptors or their expression pattern has been accumulating rapidly; however, very little is known regarding the distribution of ecto-nucleotidases in the periphery. The extracellular level of nucleotides is controlled by ecto-nucleotidases, whereby the three membrane-bound members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family are of special functional importance. Using enzyme histochemistry and immunostaining, we demonstrate that NTPDase2 is associated with nonmyelinating Schwann cells of the rat sciatic nerve, whereas NTPDase1 is restricted to blood vessel walls. NTPDase2 immunoreactivity was detected from embryonic day E18 onward, suggesting that immature Schwann cells express the enzyme. With the onset of myelination, NTPDase2 immunoreactivity remained associated solely with nonmyelinating Schwann cells. NTPDase2 was absent from perisynaptic Schwann cells but was associated with fibroblasts covering the endplate at some distance. In addition, NTPDase2 immunoreactivity was associated with the satellite glial cells in dorsal root ganglia and sympathetic ganglia, and with the enteric glia surrounding the cell bodies of ganglionic neurons of the myenteric and the submucous plexus. In contrast to NTPDase1, NTPDase2 preferentially hydrolyzes nucleoside triphosphates over nucleoside diphosphates and thus can act either in inactivating or in producing P2 receptor ligands. Our results suggest that NTPDase2 plays an important role in the control of nucleotide-mediated activation of peripheral neurons or glia and in the dialogue between these two cell types.

P2Y 2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation

“…If one were to equate nucleotide release as the molecular ''gas pedal,'' then the enzymes that hydrolyze these molecules would be the ''brake.'' Multiple ecto-nucleotidases have been identified on neurons and glia during development (51,52). The temporal and spatial abundance of nucleotidases have the potential to influence extracellular nucleotide signaling and, as suggested here, neurite formation and neuronal differentiation.…”

Cellular function and molecular structure of ecto-nucleotidases

“…It is also found on taste buds [51] and was identified in a variety of tumor cells [37]. In the rodent brain, it is highly expressed by adult neural stem cells, where it has been implicated in the generation of new nerve cells, by non-myelinating Schwann cells of the peripheral nervous system, the satellite glia of dorsal root ganglia, and enteric glia [52][53][54][55][56][57]. In Xenopus laevis, NTPDase2 together with the P2Y 1 receptor is essential for eye development [58].…”

Expression of Ecto-ATPase NTPDase2 in Human Dental Pulp

“…Cell-surface NTPDases1-3 and 8 provide the primary means for extracellular ATP degradation (Zimmermann, 2000;Kukulski et al, 2005). Expression of NTPDase2 in the nervous system and its potential roles have been explored (Braun et al, 2000(Braun et al, , 2003(Braun et al, , 2004Shukla et al, 2005;Mishra et al, 2006). However, it is not known if NTPDase2 is present in human dental pulp and provides a mechanism for ATP degradation, a necessary step for ATP signal transmission to occur.…”