{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:16:43Z","timestamp":1778505403857,"version":"3.51.4"},"reference-count":112,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cell adhesion molecule L1 is essential not only for neural development, but also for synaptic functions and regeneration after trauma in adulthood. Abnormalities in L1 functions cause developmental and degenerative disorders. L1\u2019s functions critically depend on proteolysis which underlies dynamic cell interactions and signal transduction. We showed that a 70 kDa fragment (L1-70) supports mitochondrial functions and gene transcription. To gain further insights into L1-70\u2019s functions, we investigated several binding partners. Here we show that L1-70 interacts with topoisomerase 1 (TOP1), peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2). TOP1, PPAR\u03b3 and NDUFV2 siRNAs reduced L1-dependent neurite outgrowth, and the topoisomerase inhibitors topotecan and irinotecan inhibited L1-dependent neurite outgrowth, neuronal survival and migration. In cultured neurons, L1 siRNA reduces the expression levels of the long autism genes neurexin-1 (Nrxn1) and neuroligin-1 (Nlgn1) and of the mitochondrially encoded gene NADH:ubiquinone oxidoreductase core subunit 2 (ND2). In mutant mice lacking L1-70, Nrxn1 and Nlgn1, but not ND2, mRNA levels are reduced. Since L1-70\u2019s interactions with TOP1, PPAR\u03b3 and NDUFV2 contribute to the expression of two essential long autism genes and regulate important neuronal functions, we propose that L1 may not only ameliorate neurological problems, but also psychiatric dysfunctions.<\/jats:p>","DOI":"10.3390\/ijms24032097","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T06:52:41Z","timestamp":1674197561000},"page":"2097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Interactions of the 70 kDa Fragment of Cell Adhesion Molecule L1 with Topoisomerase 1, Peroxisome Proliferator-Activated Receptor \u03b3 and NADH Dehydrogenase (Ubiquinone) Flavoprotein 2 Are Involved in Gene Expression and Neuronal L1-Dependent Functions"],"prefix":"10.3390","volume":"24","author":[{"given":"Gabriele","family":"Loers","sequence":"first","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Kleene","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Bork","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melitta","family":"Schachner","sequence":"additional","affiliation":[{"name":"Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-4614-8090-7_9","article-title":"The L1 family of cell adhesion molecules: A sickening number of mutations and protein functions","volume":"8","author":"Hortsch","year":"2014","journal-title":"Adv. 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