Abstract
The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [3H]dopamine release in concentration- and time-dependent manners. Interestingly, even though rTCTP induced the increase in intracellular calcium levels ([Ca2+]i), the rTCTP-driven effect on dopamine release was mediated by a Ca2+-independent pathway, as evidenced by the fact that Ca2+-modulating agents such as Ca2+ chelators and a voltage-gated L-type Ca2+-channel blocker did not produce any changes in rTCTP-evoked dopamine release. In a study to investigate the involvement of phospholipase A2 (PLA2) in rTCTP-induced dopamine release, the inhibitor for Ca2+-independent PLA2 (iPLA2) produced a significant inhibitory effect on rTCTP-induced dopamine release, whereas this release was not significantly inhibited by Ca2+-dependent cytosolic PLA2 (cPLA2) and secretory PLA2 (sPLA2) inhibitors. We found that rTCTP-induced dopamine release from neuronal PC12 cells was modulated by a Ca2+-independent mechanism that involved PLA2 in the process, suggesting the regulatory role of TCTP in the neuronal functions.
Highlights
The translationally controlled tumor protein (TCTP) was initially reported as a tumor-associated and growth-related protein
We investigated the novel function of TCTP in dopamine release, focusing on its Ca2+-independent regulation of neurotransmitter release in rat pheochromocytoma PC12 cells in which endogenous TCTP protein expression is detected (Figure 1)
We found that dopamine release from PC12 cells was stimulated by exogenous treatment with recombinant TCTP (rTCTP), which triggered basal dopamine release in concentration- and time-dependent manners and additively increased the high K+-stimulated dopamine release in PC12 cells (Figure 2)
Summary
The translationally controlled tumor protein (TCTP) was initially reported as a tumor-associated and growth-related protein (reviewed in [1]). TCTP has been attracted an increasing number of researchers’ attention because of its diverse biological functions and potentially important roles in medically relevant processes based on the fact that TCTP is ubiquitously expressed in a variety of different tissues and cell types, and its levels are highly regulated in response to various extracellular stimuli at both transcriptional and translational levels (reviewed in [1]). TCTP has been recognized as a multifunctional protein with diverse physiological and pathological roles in cell-cycle progression, proliferation, oncogenic tumorigenesis, stress response, gene regulation, cell death, and protection against cell death induced by heat shock stress, or oxidative stress. J.oMfofl.uSnci.c2t0io16n, 1a7l, i1m774portance have been presented [5], but its detailed role of TCTP espe2coifa1l3ly in the nervous system remains largely elusive. PTCmTRPNmARNisAeixsperxepsrseesdseidninmmanaynyaarereaassooff tthhee aadduulltthhuummananbrbarianin[6][,6a]n, dansdignsiigfincainfitclyantly decreaddseiescderaeTsaeCseTadnPdTeCxDTpoPrwesensx’ipsornesyswsnidoanrsoomwbeasse[r7ov]besdaenridvnetdihneinttheetmhsepchoteirzmaolppcohorrraetlneixcaoorhtfeippxpaotoifceanpmtasptiwuensittsh[8w]A. iltMzhhoeAriemlzhreeerci’emsnedtlriy’ss,ease and Dtorawnnsc’rsipstysnthdartomeneco[d7e] TaCnTdPinwethreefoscuhnidzotophbereenniraichheipdpinoctahme apxuosna[l8]c.omMpoarrtemreencteonftleym, btrraynosncicripts that enancoddaedTulCt TnPeuwroenrse [f9o–u12n]d, stuogbgeesetinnrgicthheatdTinCTtPhepalaxyosnaanl ciommpopratarntmt benutt ostfilel munbkrnyoownnic raonled iandult neuronseu[9ro–n1a2l]s, yssutgemgess. ting that TCTP plays an important but still unknown role in neuronal systems
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
