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Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
by
Patel, Trushar R.
, Mehlen, Patrick
, Reuten, Raphael
, Tüting, Thomas
, Poschl, Ernst
, Djonov, Valentin
, Clausen-Schaumann, Hauke
, Ehrbar, Martin
, Bald, Tobias
, Yurchenco, Peter D.
, Nikodemus, Denise
, Rama, Nicolas
, Metzger, Stéphanie
, Bloch, Wilhelm
, McKee, Karen K.
, Koch, Manuel
, Prein, Carina
, Kaltenberg, Jennifer
, Meier, Markus
, McDougall, Matthew
, Delcros, Jean-Guy
, Zhou, Zhigang
, Gibert, Benjamin
, Zigrino, Paola
, Stetefeld, Jörg
in
13
/ 13/109
/ 13/51
/ 14
/ 14/63
/ 631/378/2571/2576
/ 631/535/1266
/ 631/80/79/750
/ Angiogenesis
/ Biochemistry
/ Cancer
/ Dermatology
/ Endothelium
/ Extracellular matrix
/ Humanities and Social Sciences
/ Laboratories
/ Life Sciences
/ Membranes
/ multidisciplinary
/ Nervous system
/ Proteins
/ Research parks
/ Science
/ Science (multidisciplinary)
/ Tissue engineering
2016
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Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
by
Patel, Trushar R.
, Mehlen, Patrick
, Reuten, Raphael
, Tüting, Thomas
, Poschl, Ernst
, Djonov, Valentin
, Clausen-Schaumann, Hauke
, Ehrbar, Martin
, Bald, Tobias
, Yurchenco, Peter D.
, Nikodemus, Denise
, Rama, Nicolas
, Metzger, Stéphanie
, Bloch, Wilhelm
, McKee, Karen K.
, Koch, Manuel
, Prein, Carina
, Kaltenberg, Jennifer
, Meier, Markus
, McDougall, Matthew
, Delcros, Jean-Guy
, Zhou, Zhigang
, Gibert, Benjamin
, Zigrino, Paola
, Stetefeld, Jörg
in
13
/ 13/109
/ 13/51
/ 14
/ 14/63
/ 631/378/2571/2576
/ 631/535/1266
/ 631/80/79/750
/ Angiogenesis
/ Biochemistry
/ Cancer
/ Dermatology
/ Endothelium
/ Extracellular matrix
/ Humanities and Social Sciences
/ Laboratories
/ Life Sciences
/ Membranes
/ multidisciplinary
/ Nervous system
/ Proteins
/ Research parks
/ Science
/ Science (multidisciplinary)
/ Tissue engineering
2016
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Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
by
Patel, Trushar R.
, Mehlen, Patrick
, Reuten, Raphael
, Tüting, Thomas
, Poschl, Ernst
, Djonov, Valentin
, Clausen-Schaumann, Hauke
, Ehrbar, Martin
, Bald, Tobias
, Yurchenco, Peter D.
, Nikodemus, Denise
, Rama, Nicolas
, Metzger, Stéphanie
, Bloch, Wilhelm
, McKee, Karen K.
, Koch, Manuel
, Prein, Carina
, Kaltenberg, Jennifer
, Meier, Markus
, McDougall, Matthew
, Delcros, Jean-Guy
, Zhou, Zhigang
, Gibert, Benjamin
, Zigrino, Paola
, Stetefeld, Jörg
in
13
/ 13/109
/ 13/51
/ 14
/ 14/63
/ 631/378/2571/2576
/ 631/535/1266
/ 631/80/79/750
/ Angiogenesis
/ Biochemistry
/ Cancer
/ Dermatology
/ Endothelium
/ Extracellular matrix
/ Humanities and Social Sciences
/ Laboratories
/ Life Sciences
/ Membranes
/ multidisciplinary
/ Nervous system
/ Proteins
/ Research parks
/ Science
/ Science (multidisciplinary)
/ Tissue engineering
2016
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Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
Journal Article
Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
2016
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Overview
Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin γ1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs.
Netrins are secreted guidance factors that promote axon outgrowth and orientation during nervous system development. Here the authors present structural and biological evidence that netrin-4 is not a guidance cue per se, but rather functions to modulate laminin-laminin interactions.
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