UNC-6/Netrin and SLT-1/Slit Guidance Cues Orient Axon Outgrowth Mediated by MIG-10/RIAM/Lamellipodin

Christopher C. Quinn, Douglas S. Pfeil, Esteban Chen, Elizabeth L. Stovall, Maegan V. Harden, Megan K. Gavin, Wayne Forrester, Elizabeth F. Ryder, Martha C. Soto, William G. Wadsworth

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background: Axon migrations are guided by extracellular cues that can act as repellants or attractants. However, the logic underlying the manner through which attractive and repulsive responses are determined is unclear. Many extracellular guidance cues, and the cellular components that mediate their signals, have been implicated in both types of responses. Results: Genetic analyses indicate that MIG-10/RIAM/lamellipodin, a cytoplasmic adaptor protein, functions downstream of the attractive guidance cue UNC-6/netrin and the repulsive guidance cue SLT-1/slit to direct the ventral migration of the AVM and PVM axons in C. elegans. Furthermore, overexpression of MIG-10 in the absence of UNC-6 and SLT-1 induces a multipolar phenotype with undirected outgrowths. Addition of either UNC-6 or SLT-1 causes the neurons to become monopolar. Moreover, the ability of UNC-6 or SLT-1 to direct the axon ventrally is enhanced by the MIG-10 overexpression. We also demonstrate that an interaction between MIG-10 and UNC-34, a protein that promotes actin-filament extension, is important in the response to guidance cues and that MIG-10 colocalizes with actin in cultured cells, where it can induce the formation of lamellipodia. Conclusions: We conclude that MIG-10 mediates the guidance of AVM and PVM axons in response to the extracellular UNC-6 and SLT-1 guidance cues. The attractive and repulsive guidance cues orient MIG-10-dependant axon outgrowth to cause a directional response.

Original languageEnglish
Pages (from-to)845-853
Number of pages9
JournalCurrent Biology
Volume16
Issue number9
DOIs
StatePublished - May 9 2006

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axons
Cues
Axons
Actins
pseudopodia
attractants
microfilaments
cultured cells
Neurons
actin
Pseudopodia
Aptitude
Proteins
proteins
neurons
Cells
netrin-1
Neuronal Outgrowth
Actin Cytoskeleton
phenotype

Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Quinn, C. C., Pfeil, D. S., Chen, E., Stovall, E. L., Harden, M. V., Gavin, M. K., ... Wadsworth, W. G. (2006). UNC-6/Netrin and SLT-1/Slit Guidance Cues Orient Axon Outgrowth Mediated by MIG-10/RIAM/Lamellipodin. Current Biology, 16(9), 845-853. https://doi.org/10.1016/j.cub.2006.03.025

UNC-6/Netrin and SLT-1/Slit Guidance Cues Orient Axon Outgrowth Mediated by MIG-10/RIAM/Lamellipodin. / Quinn, Christopher C.; Pfeil, Douglas S.; Chen, Esteban; Stovall, Elizabeth L.; Harden, Maegan V.; Gavin, Megan K.; Forrester, Wayne; Ryder, Elizabeth F.; Soto, Martha C.; Wadsworth, William G.

In: Current Biology, Vol. 16, No. 9, 09.05.2006, p. 845-853.

Research output: Contribution to journalArticle

Quinn, CC, Pfeil, DS, Chen, E, Stovall, EL, Harden, MV, Gavin, MK, Forrester, W, Ryder, EF, Soto, MC & Wadsworth, WG 2006, 'UNC-6/Netrin and SLT-1/Slit Guidance Cues Orient Axon Outgrowth Mediated by MIG-10/RIAM/Lamellipodin', Current Biology, vol. 16, no. 9, pp. 845-853. https://doi.org/10.1016/j.cub.2006.03.025
Quinn, Christopher C. ; Pfeil, Douglas S. ; Chen, Esteban ; Stovall, Elizabeth L. ; Harden, Maegan V. ; Gavin, Megan K. ; Forrester, Wayne ; Ryder, Elizabeth F. ; Soto, Martha C. ; Wadsworth, William G. / UNC-6/Netrin and SLT-1/Slit Guidance Cues Orient Axon Outgrowth Mediated by MIG-10/RIAM/Lamellipodin. In: Current Biology. 2006 ; Vol. 16, No. 9. pp. 845-853.
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abstract = "Background: Axon migrations are guided by extracellular cues that can act as repellants or attractants. However, the logic underlying the manner through which attractive and repulsive responses are determined is unclear. Many extracellular guidance cues, and the cellular components that mediate their signals, have been implicated in both types of responses. Results: Genetic analyses indicate that MIG-10/RIAM/lamellipodin, a cytoplasmic adaptor protein, functions downstream of the attractive guidance cue UNC-6/netrin and the repulsive guidance cue SLT-1/slit to direct the ventral migration of the AVM and PVM axons in C. elegans. Furthermore, overexpression of MIG-10 in the absence of UNC-6 and SLT-1 induces a multipolar phenotype with undirected outgrowths. Addition of either UNC-6 or SLT-1 causes the neurons to become monopolar. Moreover, the ability of UNC-6 or SLT-1 to direct the axon ventrally is enhanced by the MIG-10 overexpression. We also demonstrate that an interaction between MIG-10 and UNC-34, a protein that promotes actin-filament extension, is important in the response to guidance cues and that MIG-10 colocalizes with actin in cultured cells, where it can induce the formation of lamellipodia. Conclusions: We conclude that MIG-10 mediates the guidance of AVM and PVM axons in response to the extracellular UNC-6 and SLT-1 guidance cues. The attractive and repulsive guidance cues orient MIG-10-dependant axon outgrowth to cause a directional response.",
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AU - Pfeil, Douglas S.

AU - Chen, Esteban

AU - Stovall, Elizabeth L.

AU - Harden, Maegan V.

AU - Gavin, Megan K.

AU - Forrester, Wayne

AU - Ryder, Elizabeth F.

AU - Soto, Martha C.

AU - Wadsworth, William G.

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