Cell surface translocation of annexin A2 facilitates Glutamate-induced extracellular proteolysis

Mallika Valapala, Sayantan Maji, Julian Borejdo, Jamboor K. Vishwanatha

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Glutamate-induced elevation in intracellular Ca2+ has been implicated in excitotoxic cell death. Neurons respond to increased glutamate levels by activating an extracellular proteolytic cascade involving the components of the plasmin-plasminogen system. AnxA2 is a Ca2+- dependent phospholipid binding protein and serves as an extracellular proteolytic center by recruiting the tissue plasminogen activator and plasminogen and mediating the localized generation of plasmin. Ratiometric Ca2+ imaging and time-lapse confocal microscopy demonstrated glutamate-induced Ca2+ influx. We showed that glutamate translocated both endogenous and AnxA2-GFP to the cell surface in a process dependent on the activity of the NMDA receptor. Glutamate-induced translocation of AnxA2 is dependent on the phosphorylation of tyrosine 23 at the N terminus, and mutation of tyrosine 23 to a non-phosphomimetic variant inhibits the translocation process. The cell surfacetranslocated AnxA2 forms an active plasmin-generating complex, and this activity can be neutralized by a hexapeptide directed against the N terminus. These results suggest an involvement of AnxA2 in potentiating glutamate-induced cell death processes.

Original languageEnglish
Pages (from-to)15915-15926
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number23
DOIs
StatePublished - 6 Jun 2014

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Annexin A2
Proteolysis
Glutamic Acid
Fibrinolysin
Plasminogen
Cell death
Tyrosine
Cell Death
Time-Lapse Imaging
Phosphorylation
Confocal microscopy
Tissue Plasminogen Activator
N-Methyl-D-Aspartate Receptors
Confocal Microscopy
Neurons
Phospholipids
Carrier Proteins
Imaging techniques
Mutation

Cite this

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Cell surface translocation of annexin A2 facilitates Glutamate-induced extracellular proteolysis. / Valapala, Mallika; Maji, Sayantan; Borejdo, Julian; Vishwanatha, Jamboor K.

In: Journal of Biological Chemistry, Vol. 289, No. 23, 06.06.2014, p. 15915-15926.

Research output: Contribution to journalArticle

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