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U.S.A."],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:p>PIN-FORMED (PIN) auxin transporters are essential for plant development, relying on asymmetric localization at the plasma membrane. While the central hydrophilic loop (HL) of PINs is known to integrate various regulatory signals, the structural basis of its coordination remains unclear. Here, we demonstrate that the PIN\u2013HL domain undergoes homotypic interaction independent of the transmembrane domains via a conserved \u03b2-sheet motif. Deleting this motif in PIN2 reinforced protein clustering and polarity, and impaired intracellular trafficking, leading to defective root gravitropism. These phenotypes were successfully reversed through rapamycin-induced reconstitution of the HL\u2013HL interaction, confirming that this physical association is vital for native PIN2 behavior. Furthermore, we show that phosphorylation of the HL domain inhibits this interaction, which in turn modulates the recruitment of PIN-regulatory factors. Our findings support a model in which the HL\u2013HL interaction serves as a regulatory hub, where phosphorylation and other modulators converge to influence PIN behavior.<\/jats:p>","DOI":"10.1073\/pnas.2620626123","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:13:32Z","timestamp":1790784812000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A conserved \u03b2-sheet motif mediates PIN2 hydrophilic loop\u2013loop interactions to regulate PIN2 dynamics"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8625-3481","authenticated-orcid":false,"given":"Kwang-Ho","family":"Maeng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Sciences, Seoul National University","place":["Seoul, Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1743-3403","authenticated-orcid":false,"given":"Hyung-Taeg","family":"Cho","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Sciences, Seoul National University","place":["Seoul, Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.181"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-12-249"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-012-0039-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05142-w"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/415806a"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013145107"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/plcell\/koab207"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.052456"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.109.072678"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.72"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2012.05030.x"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200824109"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.028365"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2310126120"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2517205122"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04883-y"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1121356"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1104\/pp.112.196139"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220205110"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/nph.16915"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00003-5"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.03.021"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001510"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808073105"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molp.2021.05.006"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1104\/pp.16.00373"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbi.2018.05.001"},{"key":"e_1_3_4_28_2","volume-title":"Additional Perspectives on Auxin Signaling","author":"Hammes U. 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