Low density lipoprotein receptor-related protein 1 mediated endocytosis of β1-integrin influences cell adhesion and cell migration

Rabiej, Verena K.; Pflanzner, Thorsten; Wagner, Timo; Goetze, Kristina; Storck, Steffen E.; Eble, Johannes A.; Weggen, Sascha; Mueller‐Klieser, Wolfgang; Pietrzik, Claus U.

doi:10.1016/j.yexcr.2015.11.020

Cited by 34 publications

(42 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An expression construct encoding an N-terminal myc tagged LRP-mini-receptor (Rabiej et al, 2015) was used for generation of a C-terminally GFP tagged LRP-mini-receptor (LRP1-GFP). After verification that the newly generated LRP1-GFP fusion protein was expressed as full-length protein and that the GFP-tag did not alter the subcellular localization (data not shown) the construct was used for live cell imaging.…”

Section: Resultsmentioning

confidence: 99%

LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

Herr

Strecker

Storck

et al. 2017

Front. Mol. Neurosci.

Self Cite

View full text Add to dashboard Cite

The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third) but to a higher degree in distinct fast axonal transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change of APP transport velocities, indicating that LRP1 recruits APP to a specific type of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated APP transport. We further show that monomeric and dimeric APP exhibit similar transport characteristics and that both are affected by LRP1 in a similar way, by slowing down APP anterograde transport and increasing its endocytosis rate. In line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an increase of monomeric and dimeric APP surface localization and in turn accelerated shedding by meprin β and ADAM10. Notably, a choroid plexus specific LRP1 knockout caused a much higher secretion of sAPP dimers into the cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1 functions as a sorting receptor for APP, regulating its cell surface localization and thereby its processing by ADAM10 and meprin β, with the latter exhibiting a preference for APP in its dimeric state.

show abstract

Section: Resultsmentioning

confidence: 99%

LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

Herr

Strecker

Storck

et al. 2017

Front. Mol. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Besides the aforementioned signaling pathways that are regulated by LRP1, other pathways are likely involved as well. For example, mouse embryonic fibroblasts or neuronal cells with a knockin mutation of LRP1’s NPxY motif that is responsible for β1-integrin interaction display impaired migratory capability (70). Given that β1-integrin plays an important role in angiogenesis by regulates VEGF signaling, focal adhesions assembly/disassembly, and cytoskeleton remodeling processes [reviewed by Avraamides et al (71)], it is possible that LRP1 regulates angiogenesis through integrin signaling.…”

Section: Discussionmentioning

confidence: 99%

Low-Density Lipoprotein Receptor-Related Protein-1 Signaling in Angiogenesis

Mao

Xie

2017

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Low-density lipoprotein receptor-related protein-1 (LRP1) plays multifunctional roles in lipid homeostasis, signaling transduction, and endocytosis. It has been recognized as an endocytic receptor for many ligands and is involved in the signaling pathways of many growth factors or cytokines. Dysregulation of LRP1-dependent signaling events contributes to the development of pathophysiologic processes such as Alzheimer’s disease, atherosclerosis, inflammation, and coagulation. Interestingly, recent studies have linked LRP1 with endothelial function and angiogenesis, which has been underappreciated for a long time. During zebrafish embryonic development, LRP1 is required for the formation of vascular network, especially for the venous development. LRP1 depletion in the mouse embryo proper leads to angiogenic defects and disruption of endothelial integrity. Moreover, in a mouse oxygen-induced retinopathy model, specific depletion of LRP1 in endothelial cells results in abnormal development of neovessels. These loss-of-function studies suggest that LRP1 plays a pivotal role in angiogenesis. The review addresses the recent advances in the roles of LRP1-dependent signaling during angiogenesis.

show abstract

“…LRP1 was shown to be involved in β1-integrin maturation, transport to the cell surface and internalization (Rabiej et al 2016; Salicioni et al 2004). Moreover, LRP1 knockout may indirectly affect integrin expression by downregulating ERK phosphorylation, as has been recently demonstrated for hematopoietic stem/progenitor cells (Wang et al 2015) At the same time different integrins are known to play role in oligodendrocyte differentiation and maturation (Baron et al 2014; Blaschuk et al 2000; Buttery and ffrench-Constant 1999; Terada et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Thereby, LRP1 modulates numerous cellular activities, including cell proliferation, migration and survival in vascular smooth muscle cells, fibroblasts, osteoblasts, keratinocytes, hepatic stellate cells or Schwann cells (Boucher and Herz 2011; Campana et al 2006; Grey et al 2006; Llorente-Cortes et al 2012; Mantuano et al 2010; Tang et al 2010). Also, the expression of LRP1 in radial glia of the adult spinal cord and the involvement of LRP1 in neuroblast migration along the rostral-migratory stream has recently been reported (Petit et al 2011; Rabiej et al 2016). Furthermore, LRP1 is responsible for amyloid precursor protein (APP)-transport and post-synaptic receptor trafficking, which underlines its essential function in the adult brain (Jaeger and Pietrzik 2008; Maier et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation

Safina

Schlitt

Romeo

et al. 2016

Glia

Self Cite

View full text Add to dashboard Cite

The LDL family of receptors and its member LRP1 have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation. In the current study we show that LeX-glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS. We have investigated the basic properties of LRP1 conditional knockout on the neural stem/progenitor cells (NSPCs) from the cortex and the spinal cord, created by means of Cre-loxp mediated recombination in vitro. The functional status of LRP1-deficient cells has been studied using proliferation, differentiation and apoptosis assays. LRP1 deficient NSPCs from both CNS regions demonstrated altered differentiation profiles. Their differentiation capacity towards oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes and neurons was reduced. In contrast, astrocyte differentiation was promoted. Moreover, LRP1 deletion had a negative effect on NSPCs proliferation and survival. Our observations suggest that LRP1 facilitates NSPCs differentiation via interaction with ApoE. Upon ApoE4 stimulation wild type NSPCs generated more oligodendrocytes, but LRP1 knockout cells showed no response. The effect of ApoE seems to be independent of cholesterol uptake, but is rather mediated by downstream MAPK and Akt activation.

show abstract

Low density lipoprotein receptor-related protein 1 mediated endocytosis of β1-integrin influences cell adhesion and cell migration

Cited by 34 publications

References 80 publications

LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

Low-Density Lipoprotein Receptor-Related Protein-1 Signaling in Angiogenesis

Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation

Contact Info

Product

Resources

About