{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:02:05Z","timestamp":1790416925429,"version":"4.1.0"},"reference-count":123,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008769","name":"Julius-Maximilians-Universit\u00e4t W\u00fcrzburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Parkinson's disease (PD) provokes bradykinesia, resting tremor, rigidity and postural instability, and also non-motor symptoms such as depression, anxiety, sleep and cognitive impairments. Similar phenotypes can be induced in Drosophila melanogaster through modification of PD-relevant genes or the administration of PD-inducing toxins. Recent studies correlated deregulation of human p21-activated kinase 4 (PAK4) with PD, leaving open the question of a causative relationship of mutations in this gene for manifestation of PD symptoms. To determine whether flies lacking the PAK4 homolog Mushroom bodies tiny (Mbt) show PD-like phenotypes, we tested for a variety of PD criteria. Here, we demonstrate that mbt mutant flies show PD-like phenotypes including age-dependent movement deficits, reduced life expectancy and fragmented sleep. They also react to a stressful situation with higher immobility, indicating an influence of Mbt on emotional behavior. Loss of Mbt function has a negative effect on the number of dopaminergic protocerebral anterior medial (PAM) neurons, most likely caused by a proliferation defect of neural progenitors. The age-dependent movement deficits are not accompanied by a corresponding further loss of PAM neurons. Previous studies highlighted the importance of a small PAM subgroup for age-dependent PD motor impairments. We show that impaired motor skills are caused by a lack of Mbt in this PAM subgroup. In addition, a broader re-expression of Mbt in PAM neurons improves life expectancy. Conversely, selective Mbt knockout in the same cells shortens lifespan. We conclude that mutations in Mbt\/PAK4 can play a causative role in the development of PD phenotypes.<\/jats:p>","DOI":"10.1242\/dmm.047811","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T07:43:36Z","timestamp":1621496616000},"source":"Crossref","is-referenced-by-count":18,"title":["Loss of p21-activated kinase Mbt\/PAK4 causes Parkinson-like phenotypes in<i>Drosophila<\/i>"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8176-443X","authenticated-orcid":false,"given":"Stephanie M.","family":"P\u00fctz","sequence":"first","affiliation":[{"name":"Medical Radiation and Cell Research, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jette","family":"Kram","sequence":"additional","affiliation":[{"name":"Medical Radiation and Cell Research, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rauh","sequence":"additional","affiliation":[{"name":"Medical Radiation and Cell Research, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Medical Radiation and Cell Research, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Toews","sequence":"additional","affiliation":[{"name":"Medical Radiation and Cell Research, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lueningschroer-Wang","sequence":"additional","affiliation":[{"name":"Neurobiology and Genetics, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Rieger","sequence":"additional","affiliation":[{"name":"Neurobiology and Genetics, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9734-4464","authenticated-orcid":false,"given":"Thomas","family":"Raabe","sequence":"additional","affiliation":[{"name":"Medical Radiation and Cell Research, Biocenter, Am Hubland, University of W\u00fcrzburg, D-97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"2021061411432265600_DMM047811C1","doi-asserted-by":"publisher","first-page":"e07046","DOI":"10.7554\/eLife.07046","article-title":"Maturation of a central brain flight circuit in Drosophila requires Fz2\/Ca(2)(+) signaling","volume":"4","author":"Agrawal","year":"2015","journal-title":"Elife"},{"key":"2021061411432265600_DMM047811C2","doi-asserted-by":"publisher","first-page":"a027730","DOI":"10.1101\/cshperspect.a027730","article-title":"Molecular mechanisms of sleep homeostasis in flies and mammals","volume":"9","author":"Allada","year":"2017","journal-title":"Cold Spring Harb. 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