ASIC subunit ratio and differential surface trafficking in the brain

Wu, Jiansheng; Xu, Yuanyuan; Jiang, Yuqing; Xu, Jiang; Hu, Youjia; Zha, Xiang-ming

doi:10.1186/s13041-016-0185-7

Cited by 42 publications

(66 citation statements)

References 53 publications

(55 reference statements)

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“…S3B). ASIC2b was not even localized in the plasma membrane alone, as previously reported (29). To test whether the N-terminus of ASIC2a has a critical region for the membrane targeting of ASIC2a, we deleted 2-37 aa from ASIC2a.…”

Section: Resultsmentioning

confidence: 85%

ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents

et al. 2016

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Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. Proton sensing by ASICs has been known to mediate pain, mechanosensation, taste transduction, learning and memory, and fear. In this study, we investigated the differential subcellular localization of ASIC2a and ASIC3 in heterologous expression systems. While ASIC2a targeted the cell surface itself, ASIC3 was mostly accumulated in the ER with partial expression in the plasma membrane. However, when ASIC3 was co-expressed with ASIC2a, its surface expression was markedly increased. By using bimolecular fluorescence complementation (BiFC) assay, we confirmed the heteromeric association between ASIC2a and ASIC3 subunits. In addition, we observed that the ASIC2a-dependent surface trafficking of ASIC3 remarkably enhanced the sustained component of the currents. Our study demonstrates that ASIC2a can increase the membrane conductance sensitivity to protons by facilitating the surface expression of ASIC3 through herteromeric assembly. [BMB Reports 2016; 49(10): 542-547]

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Section: Resultsmentioning

confidence: 85%

ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents

et al. 2016

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“…Mice (both males and females), from 4 wk to 9 mo of age, were used. We used this age range because the relative expression ratio of ASIC1a:ASIC2a:ASIC2b in mouse brain remained constant between 3 wk and 8 mo of age (21).…”

Section: Micementioning

confidence: 99%

“…All constructs were verified by sequencing. ASIC antibodies used the following: a rabbit anti-ASIC1 antibody (14) and a goat anti-ASIC1 (SC-13905; Santa Cruz, Biotechnology, Dallas, TX, USA) and rabbit anti-ASIC2 (21). Antibody specificity was verified by the lack of signals in corresponding ASIC knockout mice (14,21).…”

Section: Constructs and Reagentsmentioning

confidence: 99%

Human ASIC1a mediates stronger acid‐induced responses as compared with mouse ASICIa

Jiang

et al. 2018

FASEB j.

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Acid-sensing ion channels (ASICs) are the major proton receptor in the brain and a key mediator of acidosis-induced neuronal injuries in disease. Most of published data on ASIC function came from studies performed in mice, and relatively little is known about potential differences between human and mouse ASICs (hASIC and mASIC, respectively). This information is critical for us to better interpret the functional importance of ASICs in human disease. Here, we examined the expression of ASICs in acutely resected human cortical tissue. Compared with mouse cortex, human cortical tissue showed a similar ratio of ASIC1a:ASIC2a expression, had reduced ASIC2b level, and exhibited a higher membrane:total ratio of ASIC1a. We further investigated the mechanism for higher surface trafficking of hASIC1a in heterologous cells. A single amino acid at position 285 was critical for increased N-glycosylation and surface expression of hASIC1a. Consistent with the changes in trafficking and current, cells expressing hASIC1a or mASIC1a S285P mutant had a higher acid-activated calcium increase and exhibited worsened acidotoxicity. These data suggest that ASICs are likely to have a larger impact on acidosis-induced neuronal injuries in humans than mice, and this effect is, at least in part, a result of more efficient trafficking of hASIC1a.-Xu, Y., Jiang, Y.-Q., Li, C., He, M., Rusyniak, W. G., Annamdevula, N., Ochoa, J., Leavesley, S. J., Xu, J., Rich, T. C., Lin, M. T., Zha, X.-M. Human ASIC1a mediates stronger acid-induced responses as compared with mouse ASIC1a.

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“…The expression of ASICs in the brainstem was demonstrated previously202143 where ASIC1 protein was detected in the rat medulla by Western-blotting2043. Recently, mRNA of ASIC1a and ASIC2a was detected in NTS of neonatal rodent medulla38.…”

Section: Discussionmentioning

confidence: 87%

“…ASICs are proton-gated ion channels and are widely expressed in the brain71943. It was reported that ASICs participate in a variety of physiological and pathological processes including learning/memory, taste sense, hearing, nociception, mechanosensation, and ischemic neuronal injury456.…”

Section: Discussionmentioning

confidence: 99%

Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception

Song

Guan

Jiang

et al. 2016

Sci Rep

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The role of acid-sensing ion channels (ASICs) in the ventrolateral medulla (VLM) remains uncertain. Here, we found that ASIC1a and ASIC2 are widely expressed in rat medulla, and the expression level is higher at neonatal stage as compared to adult stage. The two ASIC subunits co-localized in medualla neurons. Furthermore, pH reduction triggered typical ASIC-type currents in the medulla, including the VLM. These currents showed a pH50 value of 6.6 and were blocked by amiloride. Based on their sensitivity to psalmotoxin 1 (PcTx1) and zinc, homomeric ASIC1a and heteromeric ASIC1a/2 channels were likely responsible for acid-mediated currents in the mouse medulla. ASIC currents triggered by pH 5 disappeared in the VLM neurons from ASIC1−/−, but not ASIC2−/− mice. Activation of ASICs in the medulla also triggered neuronal excitation. Moreover, microinjection of artificial cerebrospinal fluid at a pH of 6.5 into the VLM increased integrated phrenic nerve discharge, inspiratory time and respiratory drive in rats. Both amiloride and PcTx1 inhibited the acid-induced stimulating effect on respiration. Collectively, our data suggest that ASICs are highly expressed in the medulla including the VLM, and activation of ASICs in the VLM contributes to central chemoreception.

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ASIC subunit ratio and differential surface trafficking in the brain

Cited by 42 publications

References 53 publications

ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents

ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents

Human ASIC1a mediates stronger acid‐induced responses as compared with mouse ASICIa

Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception

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