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PMID:19052223

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Citation

Matusek, T, Gombos, R, Szécsényi, A, Sánchez-Soriano, N, Czibula, A, Pataki, C, Gedai, A, Prokop, A, Raskó, I and Mihály, J (2008) Formin proteins of the DAAM subfamily play a role during axon growth. J. Neurosci. 28:13310-9

Abstract

The regulation of growth cone actin dynamics is a critical aspect of axonal growth control. Among the proteins that are directly involved in the regulation of actin dynamics, actin nucleation factors play a pivotal role by promoting the formation of novel actin filaments. However, the essential nucleation factors in developing neurons have so far not been clearly identified. Here, we show expression data, and use true loss-of-function analysis and targeted expression of activated constructs to demonstrate that the Drosophila formin DAAM plays a critical role in axonal morphogenesis. In agreement with this finding, we show that dDAAM is required for filopodia formation at axonal growth cones. Our genetic interaction, immunoprecipitation and protein localization studies argue that dDAAM acts in concert with Rac GTPases, Profilin and Enabled during axonal growth regulation. We also show that mouse Daam1 rescues the CNS defects observed in dDAAM mutant flies to a high degree, and vice versa, that Drosophila DAAM induces the formation of neurite-like protrusions when expressed in mouse P19 cells, strongly suggesting that the function of DAAM in developing neurons has been conserved during evolution.

Links

PubMed Online version:10.1523/JNEUROSCI.2727-08.2008

Keywords

Actin Cytoskeleton/genetics; Actin Cytoskeleton/metabolism; Actin Cytoskeleton/ultrastructure; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Cell Line; Central Nervous System/cytology; Central Nervous System/embryology; Central Nervous System/metabolism; Conserved Sequence/genetics; DNA-Binding Proteins/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/embryology; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Evolution, Molecular; Female; Growth Cones/metabolism; Growth Cones/ultrastructure; Male; Mice; Mutation/genetics; Neural Pathways/cytology; Neural Pathways/embryology; Neural Pathways/metabolism; Neurites/metabolism; Neurites/ultrastructure; Neurogenesis/genetics; Profilins/metabolism; rac GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:M9MSM5

located_in

GO:0044295: axonal growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:M9MSM5

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9MSM5

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q5BII2

located_in

GO:0044295: axonal growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q5BII2

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q5BII2

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7YZA4

located_in

GO:0044295: axonal growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q7YZA4

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7YZA4

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IRY0

located_in

GO:0044295: axonal growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q8IRY0

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IRY0

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8MT16

located_in

GO:0044295: axonal growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q8MT16

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8MT16

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W5A4

located_in

GO:0044295: axonal growth cone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9W5A4

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W5A4

involved_in

GO:0050770: regulation of axonogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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