DOI: 10.1073/pnas.0307813100. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses

Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses

10.1073/pnas.0307813100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Synaptojanin 1 is a polyphosphoinositide phosphatase concentrated in presynaptic nerve terminals, where it dephosphorylates a pool of phosphatidylinositol 4,5-bisphosphate implicated in synaptic vesicle recycling. Like other proteins with a role in endocytosis, synaptojanin 1 undergoes constitutive phosphorylation in resting synapses and stimulation-dependent dephosphorylation by calcineurin. Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates synaptojanin 1 and regulates its function bothin vitroand in intact synaptosomes. Cdk5 phosphorylation inhibited the inositol 5-phosphatase activity of synaptojanin 1, whereas dephosphorylation by calcineurin stimulated such activity. The activity of synaptojanin 1 was also stimulated by its interaction with endophilin 1, its major binding partner at the synapse. Notably, Cdk5 phosphorylated serine 1144, which is adjacent to the endophilin binding site. Mutation of serine 1144 to aspartic acid to mimic phosphorylation by Cdk5 inhibited the interaction of synaptojanin 1 with endophilin 1. These results suggest that Cdk5 and calcineurin may have an antagonistic role in the regulation of synaptojanin 1 recruitment and activity, and therefore in the regulation of phosphatidylinositol 4,5-bisphosphate turnover at synapses.

Bibliography

Lee, S. Y., Wenk, M. R., Kim, Y., Nairn, A. C., & De Camilli, P. (2004). Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses. Proceedings of the National Academy of Sciences, 101(2), 546â551.

Authors 5

Sang Yoon Lee (first)
Markus R. Wenk (additional)
Yong Kim (additional)
Angus C. Nairn (additional)
Pietro De Camilli (additional)

References 54 Referenced 145

Dates

Type	When
Created	21 years, 7 months ago (Jan. 13, 2004, 1:28 p.m.)
Deposited	1 year, 7 months ago (Jan. 11, 2024, 5:09 p.m.)
Indexed	11 months, 1 week ago (Sept. 20, 2024, 11:37 a.m.)
Issued	21 years, 7 months ago (Jan. 2, 2004)
Published	21 years, 7 months ago (Jan. 2, 2004)
Published Online	21 years, 7 months ago (Jan. 2, 2004)
Published Print	21 years, 7 months ago (Jan. 13, 2004)

Funders 0

None

BibTeX

@article{Lee_2004, title={Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0307813100}, DOI={10.1073/pnas.0307813100}, number={2}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lee, Sang Yoon and Wenk, Markus R. and Kim, Yong and Nairn, Angus C. and De Camilli, Pietro}, year={2004}, month=jan, pages={546–551} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        9,
        20
      ]
    ],
    "date-time": "2024-09-20T15:37:45Z",
    "timestamp": 1726846665334
  },
  "reference-count": 54,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "2",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        1,
        13
      ]
    ]
  },
  "abstract": "<jats:p>Synaptojanin 1 is a polyphosphoinositide phosphatase concentrated in presynaptic nerve terminals, where it dephosphorylates a pool of phosphatidylinositol 4,5-bisphosphate implicated in synaptic vesicle recycling. Like other proteins with a role in endocytosis, synaptojanin 1 undergoes constitutive phosphorylation in resting synapses and stimulation-dependent dephosphorylation by calcineurin. Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates synaptojanin 1 and regulates its function both<jats:italic>in vitro</jats:italic>and in intact synaptosomes. Cdk5 phosphorylation inhibited the inositol 5-phosphatase activity of synaptojanin 1, whereas dephosphorylation by calcineurin stimulated such activity. The activity of synaptojanin 1 was also stimulated by its interaction with endophilin 1, its major binding partner at the synapse. Notably, Cdk5 phosphorylated serine 1144, which is adjacent to the endophilin binding site. Mutation of serine 1144 to aspartic acid to mimic phosphorylation by Cdk5 inhibited the interaction of synaptojanin 1 with endophilin 1. These results suggest that Cdk5 and calcineurin may have an antagonistic role in the regulation of synaptojanin 1 recruitment and activity, and therefore in the regulation of phosphatidylinositol 4,5-bisphosphate turnover at synapses.</jats:p>",
  "DOI": "10.1073/pnas.0307813100",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2004,
        1,
        13
      ]
    ],
    "date-time": "2004-01-13T18:28:06Z",
    "timestamp": 1074018486000
  },
  "page": "546-551",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 145,
  "title": "Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses",
  "prefix": "10.1073",
  "volume": "101",
  "author": [
    {
      "given": "Sang Yoon",
      "family": "Lee",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Departments of Cell Biology and Psychiatry and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510; and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021"
        }
      ]
    },
    {
      "given": "Markus R.",
      "family": "Wenk",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Cell Biology and Psychiatry and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510; and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021"
        }
      ]
    },
    {
      "given": "Yong",
      "family": "Kim",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Cell Biology and Psychiatry and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510; and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021"
        }
      ]
    },
    {
      "given": "Angus C.",
      "family": "Nairn",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Cell Biology and Psychiatry and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510; and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021"
        }
      ]
    },
    {
      "given": "Pietro",
      "family": "De Camilli",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Cell Biology and Psychiatry and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510; and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2004,
        1,
        2
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.271.5255.1533"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cellbio.14.1.231"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1388-1981(01)00165-2"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.physiol.65.092101.142517"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.85.8.2859"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.00122"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)80848-X"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(01)00548-7"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35044540"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.291.5506.1047"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0959-440X(02)00395-0"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-0854.2004.00071.x"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.114.6.1041"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01020"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/379353a0"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81649-9"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)00038-6"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.21-23-09101.2001"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.222657399"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.150.3.589"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(03)00644-5"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(03)00667-6"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)43787-8"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(97)01451-8"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.15.9625"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.19.12990"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.13.8710"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.16.8569"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.17.7.3841"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8052858"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(98)70297-0"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.49.30984"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.6.3257"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0166-2236(00)01930-5"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.281.5378.821"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "crossref",
      "first-page": "105",
      "DOI": "10.1046/j.1471-4159.2001.00049.x",
      "volume": "76",
      "year": "2001",
      "unstructured": "Cousin, M. A., Tan, T. C. & Robinson, P. J. (2001) J. Neurochem. 76, 105\u2013116.11145983",
      "journal-title": "J. Neurochem."
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ncb1020"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200308110"
    },
    {
      "key": "e_1_3_2_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M008932200"
    },
    {
      "key": "e_1_3_2_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35096019"
    },
    {
      "key": "e_1_3_2_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.21-02-00550.2001"
    },
    {
      "key": "e_1_3_2_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(03)00605-6"
    },
    {
      "key": "e_1_3_2_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF03401727"
    },
    {
      "key": "e_1_3_2_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M106338200"
    },
    {
      "key": "e_1_3_2_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.23-04-01189.2003"
    },
    {
      "key": "e_1_3_2_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(01)00456-1"
    },
    {
      "key": "e_1_3_2_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj2980395"
    },
    {
      "key": "e_1_3_2_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.37.24057"
    },
    {
      "key": "e_1_3_2_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0306-4522(02)00560-2"
    },
    {
      "key": "e_1_3_2_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M007197200"
    },
    {
      "key": "e_1_3_2_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0197-4580(95)00025-A"
    },
    {
      "key": "e_1_3_2_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.21-20-07944.2001"
    },
    {
      "key": "e_1_3_2_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(00)80828-4"
    },
    {
      "key": "e_1_3_2_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.45.32001"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0307813100",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        11
      ]
    ],
    "date-time": "2024-01-11T22:09:33Z",
    "timestamp": 1705010973000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0307813100"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        1,
        2
      ]
    ]
  },
  "references-count": 54,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          2004,
          1,
          13
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0307813100"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0307813100",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2004,
        1,
        2
      ]
    ]
  },
  "assertion": [
    {
      "value": "2004-01-02",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}