PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner
<p>Abstract</p> <p>Background</p> <p>Acid-sensing ion channel 1a (ASIC1a) is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the imp...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-12-01
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| Series: | Molecular Brain |
| Online Access: | http://www.molecularbrain.com/content/3/1/39 |
| _version_ | 1819122665519054848 |
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| author | Jin Wenying Shen Chong Jing Lan Zha Xiang-ming Xia Jun |
| author_facet | Jin Wenying Shen Chong Jing Lan Zha Xiang-ming Xia Jun |
| author_sort | Jin Wenying |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Acid-sensing ion channel 1a (ASIC1a) is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1), an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown.</p> <p>Results</p> <p>Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1.</p> <p>Conclusions</p> <p>Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.</p> |
| first_indexed | 2024-12-22T06:56:04Z |
| format | Article |
| id | doaj.art-41c928c3327b485ea192dea38ff6631c |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-22T06:56:04Z |
| publishDate | 2010-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-41c928c3327b485ea192dea38ff6631c2022-12-21T18:34:56ZengBMCMolecular Brain1756-66062010-12-01313910.1186/1756-6606-3-39PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent mannerJin WenyingShen ChongJing LanZha Xiang-mingXia Jun<p>Abstract</p> <p>Background</p> <p>Acid-sensing ion channel 1a (ASIC1a) is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1), an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown.</p> <p>Results</p> <p>Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1.</p> <p>Conclusions</p> <p>Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.</p>http://www.molecularbrain.com/content/3/1/39 |
| spellingShingle | Jin Wenying Shen Chong Jing Lan Zha Xiang-ming Xia Jun PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner Molecular Brain |
| title | PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner |
| title_full | PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner |
| title_fullStr | PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner |
| title_full_unstemmed | PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner |
| title_short | PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner |
| title_sort | pick1 regulates the trafficking of asic1a and acidotoxicity in a bar domain lipid binding dependent manner |
| url | http://www.molecularbrain.com/content/3/1/39 |
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