PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders.
The frequent comorbidity of Autism Spectrum Disorders (ASDs) with epilepsy suggests a shared underlying genetic susceptibility; several genes, when mutated, can contribute to both disorders. Recently, PRICKLE1 missense mutations were found to segregate with ASD. However, the mechanism by which mutat...
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2013
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oai:doaj.org-article:56d27ee6f5524f0d8f722b7539487b5c2021-11-18T08:43:48ZPRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders.1932-620310.1371/journal.pone.0080737https://doaj.org/article/56d27ee6f5524f0d8f722b7539487b5c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24312498/?tool=EBIhttps://doaj.org/toc/1932-6203The frequent comorbidity of Autism Spectrum Disorders (ASDs) with epilepsy suggests a shared underlying genetic susceptibility; several genes, when mutated, can contribute to both disorders. Recently, PRICKLE1 missense mutations were found to segregate with ASD. However, the mechanism by which mutations in this gene might contribute to ASD is unknown. To elucidate the role of PRICKLE1 in ASDs, we carried out studies in Prickle1(+/-) mice and Drosophila, yeast, and neuronal cell lines. We show that mice with Prickle1 mutations exhibit ASD-like behaviors. To find proteins that interact with PRICKLE1 in the central nervous system, we performed a yeast two-hybrid screen with a human brain cDNA library and isolated a peptide with homology to SYNAPSIN I (SYN1), a protein involved in synaptogenesis, synaptic vesicle formation, and regulation of neurotransmitter release. Endogenous Prickle1 and Syn1 co-localize in neurons and physically interact via the SYN1 region mutated in ASD and epilepsy. Finally, a mutation in PRICKLE1 disrupts its ability to increase the size of dense-core vesicles in PC12 cells. Taken together, these findings suggest PRICKLE1 mutations contribute to ASD by disrupting the interaction with SYN1 and regulation of synaptic vesicles.Lily PaemkaVinit B MahajanJessica M SkeieLevi P SowersSalleh N EhaidebPedro Gonzalez-AlegreToshikuni SasaokaHirotaka TaoAsuka MiyagiNaoto UenoKeizo TakaoTsuyoshi MiyakawaShu WuBenjamin W DarbroPolly J FergusonAndrew A PieperJeremiah K BrittJohn A WemmieDanielle S RuddThomas WassinkHatem El-ShantiHeather C MeffordGemma L CarvillJ Robert ManakAlexander G BassukPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e80737 (2013) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q Lily Paemka Vinit B Mahajan Jessica M Skeie Levi P Sowers Salleh N Ehaideb Pedro Gonzalez-Alegre Toshikuni Sasaoka Hirotaka Tao Asuka Miyagi Naoto Ueno Keizo Takao Tsuyoshi Miyakawa Shu Wu Benjamin W Darbro Polly J Ferguson Andrew A Pieper Jeremiah K Britt John A Wemmie Danielle S Rudd Thomas Wassink Hatem El-Shanti Heather C Mefford Gemma L Carvill J Robert Manak Alexander G Bassuk PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. |
| description |
The frequent comorbidity of Autism Spectrum Disorders (ASDs) with epilepsy suggests a shared underlying genetic susceptibility; several genes, when mutated, can contribute to both disorders. Recently, PRICKLE1 missense mutations were found to segregate with ASD. However, the mechanism by which mutations in this gene might contribute to ASD is unknown. To elucidate the role of PRICKLE1 in ASDs, we carried out studies in Prickle1(+/-) mice and Drosophila, yeast, and neuronal cell lines. We show that mice with Prickle1 mutations exhibit ASD-like behaviors. To find proteins that interact with PRICKLE1 in the central nervous system, we performed a yeast two-hybrid screen with a human brain cDNA library and isolated a peptide with homology to SYNAPSIN I (SYN1), a protein involved in synaptogenesis, synaptic vesicle formation, and regulation of neurotransmitter release. Endogenous Prickle1 and Syn1 co-localize in neurons and physically interact via the SYN1 region mutated in ASD and epilepsy. Finally, a mutation in PRICKLE1 disrupts its ability to increase the size of dense-core vesicles in PC12 cells. Taken together, these findings suggest PRICKLE1 mutations contribute to ASD by disrupting the interaction with SYN1 and regulation of synaptic vesicles. |
| format |
article |
| author |
Lily Paemka Vinit B Mahajan Jessica M Skeie Levi P Sowers Salleh N Ehaideb Pedro Gonzalez-Alegre Toshikuni Sasaoka Hirotaka Tao Asuka Miyagi Naoto Ueno Keizo Takao Tsuyoshi Miyakawa Shu Wu Benjamin W Darbro Polly J Ferguson Andrew A Pieper Jeremiah K Britt John A Wemmie Danielle S Rudd Thomas Wassink Hatem El-Shanti Heather C Mefford Gemma L Carvill J Robert Manak Alexander G Bassuk |
| author_facet |
Lily Paemka Vinit B Mahajan Jessica M Skeie Levi P Sowers Salleh N Ehaideb Pedro Gonzalez-Alegre Toshikuni Sasaoka Hirotaka Tao Asuka Miyagi Naoto Ueno Keizo Takao Tsuyoshi Miyakawa Shu Wu Benjamin W Darbro Polly J Ferguson Andrew A Pieper Jeremiah K Britt John A Wemmie Danielle S Rudd Thomas Wassink Hatem El-Shanti Heather C Mefford Gemma L Carvill J Robert Manak Alexander G Bassuk |
| author_sort |
Lily Paemka |
| title |
PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. |
| title_short |
PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. |
| title_full |
PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. |
| title_fullStr |
PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. |
| title_full_unstemmed |
PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. |
| title_sort |
prickle1 interaction with synapsin i reveals a role in autism spectrum disorders. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/56d27ee6f5524f0d8f722b7539487b5c |
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