STRAD pseudokinases regulate axogenesis and LKB1 stability

Biliana O. Veleva-Rotse; James L. Smart; Annette F. Baas; Benjamin Edmonds; Zi ming Zhao; Allyson Brown; Lillian R. Klug; Kelly Hansen; Gabrielle Reilly; Alexandria P. Gardner; Krishnaveni Subbiah; Eric A. Gaucher; Hans Clevers; Anthony P. Barnes

doi:10.1186/1749-8104-9-5

STRAD pseudokinases regulate axogenesis and LKB1 stability

Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Reilly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

18 Citaten (Scopus)

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Background: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.Results: We find that STRADα is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.Conclusions: We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability.

Originele taal-2	Engels
Artikelnummer	5
Tijdschrift	Neural Development
Volume	9
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1186/1749-8104-9-5
Status	Gepubliceerd - 4 mrt. 2014
Extern gepubliceerd	Ja

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@article{fa901d2287fb4ea3881dcc652ec50a58,

title = "STRAD pseudokinases regulate axogenesis and LKB1 stability",

abstract = "Background: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.Results: We find that STRADα is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.Conclusions: We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability.",

keywords = "Axon, LKB1, Neurodevelopment, Pseudokinase, STRAD",

author = "Veleva-Rotse, {Biliana O.} and Smart, {James L.} and Baas, {Annette F.} and Benjamin Edmonds and Zhao, {Zi ming} and Allyson Brown and Klug, {Lillian R.} and Kelly Hansen and Gabrielle Reilly and Gardner, {Alexandria P.} and Krishnaveni Subbiah and Gaucher, {Eric A.} and Hans Clevers and Barnes, {Anthony P.}",

note = "Funding Information: This work was supported by the National Institutes of Health grant (1R01NS079433-01) and a Friends of Doernbecher Award to APB, NASA Exobiology grant (NNX13AI08G) and the NASA Astrobiology Institute to EAG. We thank Drs. Magda Petryniak and Gregory Potter for providing primary oligodendrocyte cultures and Dr. Gary Banker and Barbara Smoody for advice and assistance in generating primary astrocyte cultures. We also thank Dr. William Skach as well as the members of the Gaucher, Clevers and Barnes laboratories for helpful advice and comments. We appreciate the critical comments on this manuscript provided by Drs. Soo-Kyung Lee, Gina Vaccaro, Michael Cohen and Franck Polleux.",

year = "2014",

month = mar,

day = "4",

doi = "10.1186/1749-8104-9-5",

language = "English",

volume = "9",

journal = "Neural Development",

issn = "1749-8104",

publisher = "BioMed Central Ltd.",

number = "1",

}

TY - JOUR

T1 - STRAD pseudokinases regulate axogenesis and LKB1 stability

AU - Veleva-Rotse, Biliana O.

AU - Smart, James L.

AU - Baas, Annette F.

AU - Edmonds, Benjamin

AU - Zhao, Zi ming

AU - Brown, Allyson

AU - Klug, Lillian R.

AU - Hansen, Kelly

AU - Reilly, Gabrielle

AU - Gardner, Alexandria P.

AU - Subbiah, Krishnaveni

AU - Gaucher, Eric A.

AU - Clevers, Hans

AU - Barnes, Anthony P.

N1 - Funding Information: This work was supported by the National Institutes of Health grant (1R01NS079433-01) and a Friends of Doernbecher Award to APB, NASA Exobiology grant (NNX13AI08G) and the NASA Astrobiology Institute to EAG. We thank Drs. Magda Petryniak and Gregory Potter for providing primary oligodendrocyte cultures and Dr. Gary Banker and Barbara Smoody for advice and assistance in generating primary astrocyte cultures. We also thank Dr. William Skach as well as the members of the Gaucher, Clevers and Barnes laboratories for helpful advice and comments. We appreciate the critical comments on this manuscript provided by Drs. Soo-Kyung Lee, Gina Vaccaro, Michael Cohen and Franck Polleux.

PY - 2014/3/4

Y1 - 2014/3/4

N2 - Background: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.Results: We find that STRADα is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.Conclusions: We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability.

AB - Background: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.Results: We find that STRADα is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.Conclusions: We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability.

KW - Axon

KW - LKB1

KW - Neurodevelopment

KW - Pseudokinase

KW - STRAD

UR - http://www.scopus.com/inward/record.url?scp=84897954620&partnerID=8YFLogxK

U2 - 10.1186/1749-8104-9-5

DO - 10.1186/1749-8104-9-5

M3 - Article

C2 - 24594058

AN - SCOPUS:84897954620

SN - 1749-8104

VL - 9

JO - Neural Development

JF - Neural Development

IS - 1

M1 - 5

ER -

STRAD pseudokinases regulate axogenesis and LKB1 stability

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