Dynamic and redundant regulation of LRRK2 and LRRK1 expression
<p>Abstract</p> <p>Background</p> <p>Mutations within the <it>leucine-rich repeat kinase 2 </it>(<it>LRRK2</it>) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-11-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/8/102 |
| _version_ | 1818210606541438976 |
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| author | Dawson Ted M Dawson Valina L Coombes Candice E Lorenz-Deperieux Bettina Rea Alexis Moore Darren J Biskup Saskia West Andrew B |
| author_facet | Dawson Ted M Dawson Valina L Coombes Candice E Lorenz-Deperieux Bettina Rea Alexis Moore Darren J Biskup Saskia West Andrew B |
| author_sort | Dawson Ted M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mutations within the <it>leucine-rich repeat kinase 2 </it>(<it>LRRK2</it>) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and disease provides an opportunity for deciphering molecular pathways important in neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family encoding a GTPase domain that controls intrinsic kinase activity. The expression profiles of the murine LRRK proteins have not been fully described and insufficiently characterized antibodies have produced conflicting results in the literature.</p> <p>Results</p> <p>Herein, we comprehensively evaluate twenty-one commercially available antibodies to the LRRK2 protein using mouse <it>LRRK2 </it>and human <it>LRRK2 </it>expression vectors, wild-type and <it>LRRK2</it>-null mouse brain lysates and human brain lysates. Eleven antibodies detect over-expressed human LRRK2 while four antibodies detect endogenous human LRRK2. In contrast, two antibodies recognize over-expressed mouse LRRK2 and one antibody detected endogenous mouse LRRK2. LRRK2 protein resides in both soluble and detergent soluble protein fractions. <it>LRRK2 </it>and the related <it>LRRK1 </it>genes encode low levels of expressed mRNA species corresponding to low levels of protein both during development and in adulthood with largely redundant expression profiles.</p> <p>Conclusion</p> <p>Despite previously published results, commercially available antibodies generally fail to recognize endogenous mouse LRRK2 protein; however, several antibodies retain the ability to detect over-expressed mouse LRRK2 protein. Over half of the commercially available antibodies tested detect over-expressed human LRRK2 protein and some have sufficient specificity to detect endogenous LRRK2 in human brain. The mammalian LRRK proteins are developmentally regulated in several tissues and coordinated expression suggest possible redundancy in the function between <it>LRRK1 </it>and <it>LRRK2</it>.</p> |
| first_indexed | 2024-12-12T05:19:17Z |
| format | Article |
| id | doaj.art-62932bbde14241a692b7ca2ddd7fd417 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-12T05:19:17Z |
| publishDate | 2007-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-62932bbde14241a692b7ca2ddd7fd4172022-12-22T00:36:40ZengBMCBMC Neuroscience1471-22022007-11-018110210.1186/1471-2202-8-102Dynamic and redundant regulation of LRRK2 and LRRK1 expressionDawson Ted MDawson Valina LCoombes Candice ELorenz-Deperieux BettinaRea AlexisMoore Darren JBiskup SaskiaWest Andrew B<p>Abstract</p> <p>Background</p> <p>Mutations within the <it>leucine-rich repeat kinase 2 </it>(<it>LRRK2</it>) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and disease provides an opportunity for deciphering molecular pathways important in neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family encoding a GTPase domain that controls intrinsic kinase activity. The expression profiles of the murine LRRK proteins have not been fully described and insufficiently characterized antibodies have produced conflicting results in the literature.</p> <p>Results</p> <p>Herein, we comprehensively evaluate twenty-one commercially available antibodies to the LRRK2 protein using mouse <it>LRRK2 </it>and human <it>LRRK2 </it>expression vectors, wild-type and <it>LRRK2</it>-null mouse brain lysates and human brain lysates. Eleven antibodies detect over-expressed human LRRK2 while four antibodies detect endogenous human LRRK2. In contrast, two antibodies recognize over-expressed mouse LRRK2 and one antibody detected endogenous mouse LRRK2. LRRK2 protein resides in both soluble and detergent soluble protein fractions. <it>LRRK2 </it>and the related <it>LRRK1 </it>genes encode low levels of expressed mRNA species corresponding to low levels of protein both during development and in adulthood with largely redundant expression profiles.</p> <p>Conclusion</p> <p>Despite previously published results, commercially available antibodies generally fail to recognize endogenous mouse LRRK2 protein; however, several antibodies retain the ability to detect over-expressed mouse LRRK2 protein. Over half of the commercially available antibodies tested detect over-expressed human LRRK2 protein and some have sufficient specificity to detect endogenous LRRK2 in human brain. The mammalian LRRK proteins are developmentally regulated in several tissues and coordinated expression suggest possible redundancy in the function between <it>LRRK1 </it>and <it>LRRK2</it>.</p>http://www.biomedcentral.com/1471-2202/8/102 |
| spellingShingle | Dawson Ted M Dawson Valina L Coombes Candice E Lorenz-Deperieux Bettina Rea Alexis Moore Darren J Biskup Saskia West Andrew B Dynamic and redundant regulation of LRRK2 and LRRK1 expression BMC Neuroscience |
| title | Dynamic and redundant regulation of LRRK2 and LRRK1 expression |
| title_full | Dynamic and redundant regulation of LRRK2 and LRRK1 expression |
| title_fullStr | Dynamic and redundant regulation of LRRK2 and LRRK1 expression |
| title_full_unstemmed | Dynamic and redundant regulation of LRRK2 and LRRK1 expression |
| title_short | Dynamic and redundant regulation of LRRK2 and LRRK1 expression |
| title_sort | dynamic and redundant regulation of lrrk2 and lrrk1 expression |
| url | http://www.biomedcentral.com/1471-2202/8/102 |
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