NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis.
AP-2 is the core-organizing element in clathrin-mediated endocytosis. During the formation of clathrin-coated vesicles, clathrin and endocytic accessory proteins interact with AP-2 in a temporally and spatially controlled manner, yet it remains elusive as to how these interactions are regulated. Her...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-10-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC3794858?pdf=render |
| _version_ | 1818620205931167744 |
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| author | Brigitte Ritter Sebastian Murphy Hatem Dokainish Martine Girard Manasa V Gudheti Guennadi Kozlov Marilene Halin Jacynthe Philie Erik M Jorgensen Kalle Gehring Peter S McPherson |
| author_facet | Brigitte Ritter Sebastian Murphy Hatem Dokainish Martine Girard Manasa V Gudheti Guennadi Kozlov Marilene Halin Jacynthe Philie Erik M Jorgensen Kalle Gehring Peter S McPherson |
| author_sort | Brigitte Ritter |
| collection | DOAJ |
| description | AP-2 is the core-organizing element in clathrin-mediated endocytosis. During the formation of clathrin-coated vesicles, clathrin and endocytic accessory proteins interact with AP-2 in a temporally and spatially controlled manner, yet it remains elusive as to how these interactions are regulated. Here, we demonstrate that the endocytic protein NECAP 1, which binds to the α-ear of AP-2 through a C-terminal WxxF motif, uses an N-terminal PH-like domain to compete with clathrin for access to the AP-2 β2-linker, revealing a means to allow AP-2-mediated coordination of accessory protein recruitment and clathrin polymerization at sites of vesicle formation. Knockdown and functional rescue studies demonstrate that through these interactions, NECAP 1 and AP-2 cooperate to increase the probability of clathrin-coated vesicle formation and to control the number, size, and cargo content of the vesicles. Together, our data demonstrate that NECAP 1 modulates the AP-2 interactome and reveal a new layer of organizational control within the endocytic machinery. |
| first_indexed | 2024-12-16T17:49:41Z |
| format | Article |
| id | doaj.art-83c6795f781d4dc4a2e3098549248965 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-16T17:49:41Z |
| publishDate | 2013-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-83c6795f781d4dc4a2e30985492489652022-12-21T22:22:21ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852013-10-011110e100167010.1371/journal.pbio.1001670NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis.Brigitte RitterSebastian MurphyHatem DokainishMartine GirardManasa V GudhetiGuennadi KozlovMarilene HalinJacynthe PhilieErik M JorgensenKalle GehringPeter S McPhersonAP-2 is the core-organizing element in clathrin-mediated endocytosis. During the formation of clathrin-coated vesicles, clathrin and endocytic accessory proteins interact with AP-2 in a temporally and spatially controlled manner, yet it remains elusive as to how these interactions are regulated. Here, we demonstrate that the endocytic protein NECAP 1, which binds to the α-ear of AP-2 through a C-terminal WxxF motif, uses an N-terminal PH-like domain to compete with clathrin for access to the AP-2 β2-linker, revealing a means to allow AP-2-mediated coordination of accessory protein recruitment and clathrin polymerization at sites of vesicle formation. Knockdown and functional rescue studies demonstrate that through these interactions, NECAP 1 and AP-2 cooperate to increase the probability of clathrin-coated vesicle formation and to control the number, size, and cargo content of the vesicles. Together, our data demonstrate that NECAP 1 modulates the AP-2 interactome and reveal a new layer of organizational control within the endocytic machinery.http://europepmc.org/articles/PMC3794858?pdf=render |
| spellingShingle | Brigitte Ritter Sebastian Murphy Hatem Dokainish Martine Girard Manasa V Gudheti Guennadi Kozlov Marilene Halin Jacynthe Philie Erik M Jorgensen Kalle Gehring Peter S McPherson NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. PLoS Biology |
| title | NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. |
| title_full | NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. |
| title_fullStr | NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. |
| title_full_unstemmed | NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. |
| title_short | NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. |
| title_sort | necap 1 regulates ap 2 interactions to control vesicle size number and cargo during clathrin mediated endocytosis |
| url | http://europepmc.org/articles/PMC3794858?pdf=render |
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