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Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their downstream pathways remains elusive. Subcellular compartmentation has emerged as a flexible strategy to reach such a specificity. Here, we show that point contact-restricted cAMP signals control ephrin-A5-evoked axon repulsion in vitro by modulating focal adhesion kinase (FAK; also known as PTK2) phosphorylation and the assembly and disassembly rate of point contacts. Consistent with this, preventing point contact-specific cAMP signals in developing retinal ganglion cells in vivo alters the refinement of their terminal axonal arbor in the brain. Altogether, our study identifies point contacts as a compartment containing a local cAMP signal required for ephrin-A5-dependent axon guidance and highlights the crucial role of such subcellularly restricted second messenger signals in the wiring of neuronal circuits.<\/jats:p>","DOI":"10.1242\/jcs.263480","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T03:39:41Z","timestamp":1736307581000},"source":"Crossref","is-referenced-by-count":3,"title":["Point contact-restricted cAMP signaling controls ephrin-A5-induced axon repulsion"],"prefix":"10.1242","volume":"138","author":[{"given":"Johann","family":"B\u00e9cret","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision 1 , F-75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Gomez-Bravo","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision 1 , F-75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Michaud","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision 1 , F-75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlem","family":"Assali","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut du Fer \u00e0 Moulin 2 , 17 rue du Fer \u00e0 Moulin, F-75005 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efg A. 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