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The \u201cCell Wall Integrity\u201d pathway (CWI) detects cell wall defects and promotes cell wall thickening or repair to protect cell integrity. However, cell walls must be removed at contact sites between fusing cells during mating or mycelium formation. Here, we show that in Saccharomyces cerevisiae, the CWI is downregulated specifically at the contact site between mating cells. A key component of the CWI, Pkc1, accumulated at polarity sites (shmoo tips) in cells exposed to mating pheromone, but not at contact sites. Pkc1 exclusion required a cell wall protein, Fig2, induced by pheromone. In mutants lacking Fig2, cell wall removal was delayed, blocked, or even reversed after transient fusion, leading to reduced mating. These results suggest that Fig2 designates the contact site as a \u201csafe\u201d spot to degrade the cell wall.<\/jats:p>","DOI":"10.1083\/jcb.202508068","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:21:28Z","timestamp":1774678888000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Regulation of the Cell Wall Integrity pathway at the contact site between mating partners in yeast"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1914-9847","authenticated-orcid":true,"given":"Erin R.","family":"Curtis","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Massachusetts Institute of Technology 1 Biology Department, , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1764-7236","authenticated-orcid":true,"given":"Aarshi","family":"Jain","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Massachusetts Institute of Technology 1 Biology Department, , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-3585","authenticated-orcid":true,"given":"Daniel J.","family":"Lew","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Massachusetts Institute of Technology 1 Biology Department, , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"2026043009404240600_bib1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/0014-5793(91)80930-2","article-title":"Osmoregulation in Saccharomyces cerevisiae. 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