Delta1 family members are involved in filopodial actin formation and neuronal cell migration independent of Notch signaling.
Delta family proteins are transmembrane molecules that bind Notch receptors and activate downstream signaling events in neighboring cells. In addition to serving as Notch ligands, Notch-independent roles for Delta have been suggested but are not fully understood. Here, we demonstrate a previously unrecognized role for Delta in filopodial actin formation. Delta1 and Delta4, but not Delta3, exhibit filopodial protrusive activity, and this activity is independent of Notch signaling. The filopodial activity of Delta1 does not depend on the PDZ-binding domain at the C-terminus; however, the intracellular membrane-proximal region that is anchored to the plasma membrane plays an important role in filopodial activity. We further identified a Notch-independent role of DeltaD in neuronal cell migration in zebrafish. These findings suggest a possible functional link between Notch-independent filopodial activity of Delta and the control of cell motility.
Sugiyama
Kazuya
K
Graduate School of Science, Nagoya University, Nagoya, Aichi 464-8602, Japan.
Nishide
Kenji
K
Matsuo
Hiromi
H
Okigawa
Sayumi
S
Okano
Makoto
M
Ishitani
Tohru
T
Matsumoto
Kunihiro
K
Itoh
Motoyuki
M
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000254:growth & development
D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein