LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization

Grote, Alexander; Robens, Barbara K.; Blümcke, Ingmar; Becker, Albert; Schoch, Susanne; Gembé, Eva

doi:10.1016/j.nbd.2015.11.021

Cited by 12 publications

(17 citation statements)

References 20 publications

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“…Many transmembrane proteins, such as MIG-13/Lrp12, regulate actin dynamics through the WASP/WAVE pathway. Loss of Lrp12 in mouse primary neuron culture causes impaired neurite branching [62]. However, the mechanistic connections between MIG-13/Lrp2 and actin cytoskeleton remain elusive.…”

Section: New Regulators Of Actin Cytoskeleton During Neurodevelopmentmentioning

confidence: 99%

Shaping neurodevelopment: distinct contributions of cytoskeletal proteins

Tang

Jin

2018

Current Opinion in Neurobiology

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Development of a neuron critically depends on the organization of its cytoskeleton. Cytoskeletal components, such as tubulins and actins, have the remarkable ability to organize themselves into filaments and networks to support specialized and compartmentalized functions. Alterations in cytoskeletal proteins have long been associated with a variety of neurodevelopmental disorders. This review focuses on recent findings, primarily from forward genetic screens in Caenorhabditis elegans that illustrate how different tubulin protein isotypes can play distinct roles in neuronal development and function. Additionally, we discuss studies revealing new regulators of the actin cytoskeleton, and highlight recent technological advances in in vivo imaging and functional dissection of the neuronal cytoskeleton.

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Section: New Regulators Of Actin Cytoskeleton During Neurodevelopmentmentioning

confidence: 99%

Shaping neurodevelopment: distinct contributions of cytoskeletal proteins

Tang

Jin

2018

Current Opinion in Neurobiology

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“…While mice lacking Lrp5 (Fujino et al, 2003 ), Ldlr (Shimada et al, 1996 ), Apoer2 or Vldlr (Trommsdorff et al, 1999 ), or the distant member SorLA (Andersen et al, 2005 ) survive, they all have abnormalities in cholesterol homeostasis and/or brain development. Of the most distant relatives, gene silencing of Lrp12 leads to defects in brain lamination (Grote et al, 2016 ), yet to date in vivo knockouts or knockdowns of the more distant members Lrp3, Lrp10 and Lrad3 have not been reported.…”

Section: Lipoprotein Receptorsmentioning

confidence: 99%

“…It is also involved in tumorigenesis including epilepsy-associated gangliogliomas (Garnis et al, 2004 ; Robens et al, 2016 ). Silencing of Lrp12 in primary neurons leads to increased dendritic branching, silencing of Lrp12 in the mouse brain during brain development leads to cortical dyslamination and seizure sensitization (Grote et al, 2016 ). As of today, no role in AD has been described.…”

Section: Very Distinct and Short Receptors Containing Lbrsmentioning

confidence: 99%

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Functional Roles of the Interaction of APP and Lipoprotein Receptors

Pohlkamp

Wasser

Herz

2017

Front. Mol. Neurosci.

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The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD.

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“…While the anterior guidance cue remains unclear, QR.x cells appear to perceive the signal through an evolutionarily conserved transmembrane protein, MIG-13 (10,11). The mouse MIG-13 homolog Lrp12 (low-density lipoprotein receptor-related protein 12) is expressed in migrating neurons in the neocortex, and Lrp12 inhibition causes defective corticogenesis and seizure sensitization (12,13). We recently defined two semiredundant pathways in which MIG-13 signals through the actin nucleation-promoting factors WAVE and WASP to promote Arp2/3-stimulated actin polymerization at the leading edge (14).…”

mentioning

confidence: 99%

Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration

Zhu

Chai

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration inCaenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1–dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.

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LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization

Cited by 12 publications

References 20 publications

Shaping neurodevelopment: distinct contributions of cytoskeletal proteins

Shaping neurodevelopment: distinct contributions of cytoskeletal proteins

Functional Roles of the Interaction of APP and Lipoprotein Receptors

Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration

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