Stac protein (named for its SH3 and cysteine rich domains) was first identified in brain 20 years ago, and is currently known to exist in three isoforms with specific tissue expression profiles. Transcripts for Stac1 and Stac2 are found in the cerebellum, forebrain, and eye, whereas transcripts for Stac3 are found at high levels in skeletal muscle and at low levels in the same three neuronally rich regions. However, the neuronal functions of Stac have been little investigated. Here, we tested the effects of Stac on currents via neuronal high-voltage-activated Ca2+ channels expressed together with their auxiliary subunits (β2a, α2-δ1) in tsA201 cells. As described previously by others, we observed Ca2+ entry-dependent inactivation (CDI) for CaV1.2 and CaV1.3 (the predominant, neuronal L-type Ca2+ channels), and for the P/Q-type Ca2+ channel CaV2.1. CDI for CaV1.2 and CaV1.3 was suppressed almost completely by all three Stac isoforms, whereas CDI for CaV2.1 was not detectably altered. CDI is thought to depend on CaM constitutively bound to the CaV C-terminus, but based on co-expression of fluorescently tagged CaV1.2 and CaM, the Stac-caused suppression of CDI did not involve the loss of bound CaM. Expression of CaV1.2 without auxiliary subunits resulted in small amplitude currents. These small amplitude currents displayed CDI which was similar to that when β2a and α2-δ1 were also present, and which was suppressed by all three Stac isoforms. Thus, the Stac proteins appear to bind directly to CaV1.2 (and most likely to CaV1.3 as well) and to interfere with CDI without displacing CaM. Our results indicate that one likely function of neuronal Stac proteins is to tune Ca2+ entry via L-type channels. Supported by grants from NIH (AR052354 and AR070298) and MDA (176448) to KGB.

Polster, A., Perni, S., Beam, K.G. (2017). Stac Proteins Suppress Calcium Dependent Inactivation of Neuronal L-Type Ca2+ Channels. BIOPHYSICAL JOURNAL, 112(3), 245A-245A [10.1016/j.bpj.2016.11.1339].

Stac Proteins Suppress Calcium Dependent Inactivation of Neuronal L-Type Ca2+ Channels

Perni, S.;
2017

Abstract

Stac protein (named for its SH3 and cysteine rich domains) was first identified in brain 20 years ago, and is currently known to exist in three isoforms with specific tissue expression profiles. Transcripts for Stac1 and Stac2 are found in the cerebellum, forebrain, and eye, whereas transcripts for Stac3 are found at high levels in skeletal muscle and at low levels in the same three neuronally rich regions. However, the neuronal functions of Stac have been little investigated. Here, we tested the effects of Stac on currents via neuronal high-voltage-activated Ca2+ channels expressed together with their auxiliary subunits (β2a, α2-δ1) in tsA201 cells. As described previously by others, we observed Ca2+ entry-dependent inactivation (CDI) for CaV1.2 and CaV1.3 (the predominant, neuronal L-type Ca2+ channels), and for the P/Q-type Ca2+ channel CaV2.1. CDI for CaV1.2 and CaV1.3 was suppressed almost completely by all three Stac isoforms, whereas CDI for CaV2.1 was not detectably altered. CDI is thought to depend on CaM constitutively bound to the CaV C-terminus, but based on co-expression of fluorescently tagged CaV1.2 and CaM, the Stac-caused suppression of CDI did not involve the loss of bound CaM. Expression of CaV1.2 without auxiliary subunits resulted in small amplitude currents. These small amplitude currents displayed CDI which was similar to that when β2a and α2-δ1 were also present, and which was suppressed by all three Stac isoforms. Thus, the Stac proteins appear to bind directly to CaV1.2 (and most likely to CaV1.3 as well) and to interfere with CDI without displacing CaM. Our results indicate that one likely function of neuronal Stac proteins is to tune Ca2+ entry via L-type channels. Supported by grants from NIH (AR052354 and AR070298) and MDA (176448) to KGB.
Polster, A., Perni, S., Beam, K.G. (2017). Stac Proteins Suppress Calcium Dependent Inactivation of Neuronal L-Type Ca2+ Channels. BIOPHYSICAL JOURNAL, 112(3), 245A-245A [10.1016/j.bpj.2016.11.1339].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/1215795