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Compared to other G\u03b1 members, G\u03b1qGTP activates many crucial effectors, including PLC\u03b2 (Phospholipase C\u03b2) and Rho GEFs (Rho guanine nucleotide exchange factors). PLC\u03b2 regulates many key processes, such as hematopoiesis, synaptogenesis, and cell cycle, and is therefore implicated in terminal - debilitating diseases, including cancer, epilepsy, Huntington\u2019s Disease, and Alzheimer\u2019s Disease. However, due to a lack of genetic and pharmacological tools, examining how the dynamic regulation of PLC\u03b2 signaling controls cellular physiology has been difficult. Since activated PLC\u03b2 induces several abrupt cellular changes, including cell morphology, examining how the other pathways downstream of Gq-GPCRs contribute to the overall signaling has also been difficult. Here we show the engineering, validation, and application of a highly selective and efficient optogenetic inhibitor (Opto-dHTH) to completely disrupt G\u03b1qGTP-PLC\u03b2 interactions reversibly in user-defined cellular-subcellular regions on optical command. Using this newly gained PLC\u03b2 signaling control, our data indicate that the molecular competition between RhoGEFs and PLC\u03b2 for G\u03b1qGTP determines the potency of Gq-GPCR-governed directional cell migration.<\/jats:p>","DOI":"10.1101\/2023.08.10.552801","type":"posted-content","created":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T17:10:10Z","timestamp":1691860210000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal optical control of G\u03b1q-PLC\u03b2 interactions"],"prefix":"10.64898","author":[{"given":"Sithurandi","family":"Ubeysinghe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinesh","family":"Kankanamge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-8575","authenticated-orcid":false,"given":"Waruna","family":"Thotamune","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhanushan","family":"Wijayaratna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Thomas M.","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-2015","authenticated-orcid":false,"given":"Ajith","family":"Karunarathne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023081607450780000_2023.08.10.552801v1.1","doi-asserted-by":"publisher","DOI":"10.4161\/psb.4.10.9530"},{"key":"2023081607450780000_2023.08.10.552801v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0020013"},{"key":"2023081607450780000_2023.08.10.552801v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02775-8"},{"key":"2023081607450780000_2023.08.10.552801v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0049-3"},{"key":"2023081607450780000_2023.08.10.552801v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"2023081607450780000_2023.08.10.552801v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.109947"},{"key":"2023081607450780000_2023.08.10.552801v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.08.002"},{"key":"2023081607450780000_2023.08.10.552801v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.11.005"},{"key":"2023081607450780000_2023.08.10.552801v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.01.010"},{"key":"2023081607450780000_2023.08.10.552801v1.10","doi-asserted-by":"publisher","DOI":"10.1124\/mol.113.087403"},{"key":"2023081607450780000_2023.08.10.552801v1.11","doi-asserted-by":"crossref","first-page":"100702","DOI":"10.1016\/j.jbc.2021.100702","article-title":"Dissociation of the G protein betagamma from the Gq-PLCbeta complex partially attenuates PIP2 hydrolysis","volume":"296","year":"2021","journal-title":"J Biol Chem"},{"issue":"Suppl 1","key":"2023081607450780000_2023.08.10.552801v1.12","first-page":"398","article-title":"Metabolism of diacylglycerol in humans","volume":"16","year":"2007","journal-title":"Asia Pac J Clin Nutr"},{"key":"2023081607450780000_2023.08.10.552801v1.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00647.x"},{"key":"2023081607450780000_2023.08.10.552801v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.12.016"},{"key":"2023081607450780000_2023.08.10.552801v1.15","first-page":"14","article-title":"Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Galpha\/q,11","volume":"2","year":"2015","journal-title":"Front Cardiovasc Med"},{"key":"2023081607450780000_2023.08.10.552801v1.16","doi-asserted-by":"crossref","unstructured":"Schmidt, S. 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