Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration

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Zhiwen Zhu1,2,3,4, Yongping Chai1,2,3,4, Huifang Hu2

  • 1Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.

Proceedings of the National Academy of Sciences of the United States of America
|June 10, 2020
PubMed

Insights

A tyrosine kinase, SRC-1, promotes cell migration by phosphorylating MIG-13. A phosphatase, PTP-3, restricts this activity to ensure directional cell movement.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Directional cell migration is crucial for development and relies on precise regulation of actin dynamics.
  • Proteins like MIG-13/Lrp12 are involved in guiding cell movement through actin assembly.
  • Understanding the signaling pathways that control cell polarity is essential.

Purpose of the Study:

  • To investigate the role of tyrosine kinase SRC-1 in regulating MIG-13/Lrp12 activity during neuroblast migration.
  • To elucidate the function of tyrosine phosphatase PTP-3 in maintaining F-actin polarity and directional cell migration.
  • To determine how SRC-1 and PTP-3 interact to control MIG-13/Lrp12 localization and activity.

Main Methods:

  • Utilized GFP knockin animals to visualize the distribution of SRC-1 and MIG-13.
  • Performed in vitro biochemical assays with recombinant PTP-3 to assess its dephosphorylation activity on MIG-13.
  • Examined the localization of endogenous PTP-3 in migrating neuroblasts.
  • Assessed the necessity of PTP-3's extracellular domain for directional migration.

Main Results:

  • SRC-1 directly phosphorylates MIG-13, enhancing its actin assembly-promoting activity at the leading edge.
  • SRC-1 and MIG-13 are distributed throughout the plasma membrane of migrating cells.
  • PTP-3 dephosphorylates SRC-1-phosphorylated MIG-13 in vitro.
  • Endogenous PTP-3 localizes to the rear of migrating neuroblasts and is essential for directional migration.
  • PTP-3 restricts MIG-13/Lrp12 activity to ensure proper cell polarity.

Conclusions:

  • SRC-1 acts as a positive regulator of MIG-13/Lrp12 activity, promoting actin assembly for cell migration.
  • PTP-3 acts as a spatial regulator, dephosphorylating MIG-13/Lrp12 at the rear to maintain polarity.
  • The interplay between SRC-1 and PTP-3 ensures asymmetric receptor activity, guiding directional neuroblast migration.
Keywords:
cell polaritycytoskeletondirectional cell migrationtyrosine kinase and phosphatase

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