PMID- 19223396
OWN - NLM
STAT- MEDLINE
DCOM- 20090615
LR  - 20201209
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 122
IP  - Pt 6
DP  - 2009 Mar 15
TI  - Memo is a cofilin-interacting protein that influences PLCgamma1 and cofilin 
      activities, and is essential for maintaining directionality during ErbB2-induced 
      tumor-cell migration.
PG  - 787-97
LID - 10.1242/jcs.032094 [doi]
AB  - Heregulin (HRG) activates ErbB2-ErbB3 heterodimers thereby stimulating many 
      cellular responses, including motility. Memo and PLCgamma1 interact with ErbB2 
      autophosphorylation sites and are essential for HRG-induced chemotaxis. By 
      tracing HRG-stimulated cell migration in Dunn chambers, we found that Memo- or 
      PLCgamma1 knockdown (KD) strongly impairs cell directionality. Memo has no 
      obvious enzymatic activity and was discovered via its ability to complex with 
      ErbB2. Using the yeast two-hybrid approach to gain insight into Memo function, an 
      interaction between Memo and cofilin, a regulator of actin dynamics, was 
      uncovered. The interaction was confirmed in vitro using recombinant proteins and 
      in vivo in co-immunoprecipitation experiments where Memo was detected in 
      complexes with cofilin, ErbB2 and PLCgamma1. Interestingly, in Memo KD cells, 
      HRG-induced PLCgamma1 phosphorylation was decreased, suggesting that Memo 
      regulates PLCgamma1 activation. Furthermore, HRG-induced recruitment of 
      GFP-cofilin to lamellipodia is impaired in Memo and in PLCgamma1 KD cells, 
      suggesting that both proteins lie upstream of cofilin in models of ErbB2-driven 
      tumor-cell migration. Finally, in vitro F-actin binding and depolymerization 
      assays showed that Memo enhances cofilin depolymerizing and severing activity. In 
      summary, these data indicate that Memo also regulates actin dynamics by 
      interacting with cofilin and enhancing its function.
FAU - Meira, Maria
AU  - Meira M
AD  - Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 
      Basel, Switzerland.
FAU - Masson, Regis
AU  - Masson R
FAU - Stagljar, Igor
AU  - Stagljar I
FAU - Lienhard, Susanne
AU  - Lienhard S
FAU - Maurer, Francisca
AU  - Maurer F
FAU - Boulay, Anne
AU  - Boulay A
FAU - Hynes, Nancy E
AU  - Hynes NE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090217
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actin Depolymerizing Factors)
RN  - 0 (Actins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (MEMO1 protein, human)
RN  - 0 (Neuregulin-1)
RN  - 0 (Nonheme Iron Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Actin Depolymerizing Factors/*metabolism
MH  - Actins/metabolism
MH  - Biological Assay
MH  - Breast Neoplasms/enzymology/pathology
MH  - Cell Line, Tumor
MH  - *Cell Movement/drug effects
MH  - Chemotaxis/drug effects
MH  - Enzyme Activation/drug effects
MH  - Green Fluorescent Proteins/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Neoplasms/*enzymology/*pathology
MH  - Neuregulin-1/pharmacology
MH  - Nonheme Iron Proteins/*metabolism
MH  - Phospholipase C gamma/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Binding/drug effects
MH  - Protein Transport/drug effects
MH  - Pseudopodia/drug effects/enzymology
MH  - Receptor, ErbB-2/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
EDAT- 2009/02/19 09:00
MHDA- 2009/06/16 09:00
CRDT- 2009/02/19 09:00
PHST- 2009/02/19 09:00 [entrez]
PHST- 2009/02/19 09:00 [pubmed]
PHST- 2009/06/16 09:00 [medline]
AID - jcs.032094 [pii]
AID - 10.1242/jcs.032094 [doi]
PST - ppublish
SO  - J Cell Sci. 2009 Mar 15;122(Pt 6):787-97. doi: 10.1242/jcs.032094. Epub 2009 Feb 
      17.