Drosophila neural precursor cells divide asymmetrically by segregating the Numb protein into one of the two daughter cells. Numb is uniformly cortical in interphase but assumes a polarized localization in mitosis. Here, we show that a phosphorylation cascade triggered by the activation of Aurora-A is responsible for the asymmetric localization of Numb in mitosis. Aurora-A phosphorylates Par-6, a regulatory subunit of atypical protein kinase C (aPKC). This activates aPKC, which initially phosphorylates Lethal (2) giant larvae (Lgl), a cytoskeletal protein that binds and inhibits aPKC during interphase. Phosphorylated Lgl is released from aPKC and thereby allows the PDZ domain protein Bazooka to enter the complex. This changes substrate specificity and allows aPKC to phosphorylate Numb and release the protein from one side of the cell cortex. Our data reveal a molecular mechanism for the asymmetric localization of Numb and show how cell polarity can be coupled to cell-cycle progression.
机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Lee, Cheng-Yu
Andersen, Ryan O.
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Andersen, Ryan O.
Cabernard, Clemens
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Cabernard, Clemens
Manning, Laurina
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Manning, Laurina
Tran, Khoa D.
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Tran, Khoa D.
Lanskey, Marcus J.
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Lanskey, Marcus J.
Bashirullah, Arash
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Bashirullah, Arash
Doe, Chris Q.
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Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Lu, BW
Ackerman, L
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机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Ackerman, L
Jan, LY
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机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Jan, LY
Jan, YN
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Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
机构:
Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
Peng, CY
Manning, L
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Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
Manning, L
Albertson, R
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Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
Albertson, R
Doe, CQ
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Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Lee, Cheng-Yu
Andersen, Ryan O.
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h-index: 0
机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Andersen, Ryan O.
Cabernard, Clemens
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h-index: 0
机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Cabernard, Clemens
Manning, Laurina
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h-index: 0
机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Manning, Laurina
Tran, Khoa D.
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h-index: 0
机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Tran, Khoa D.
Lanskey, Marcus J.
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Lanskey, Marcus J.
Bashirullah, Arash
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机构:Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
Bashirullah, Arash
Doe, Chris Q.
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h-index: 0
机构:
Univ Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci & Mol Biol, Eugene, OR 97403 USA
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Lu, BW
Ackerman, L
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Ackerman, L
Jan, LY
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
Jan, LY
Jan, YN
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USAUniv Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
机构:
Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
Peng, CY
Manning, L
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h-index: 0
机构:
Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
Manning, L
Albertson, R
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h-index: 0
机构:
Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA
Albertson, R
Doe, CQ
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机构:
Univ Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USAUniv Oregon, Howard Hughes Med Inst, Inst Neurosci, Inst Mol Biol, Eugene, OR 97403 USA