Functions of the multi‐interacting protein KIDINS220/ARMS in cancer and other pathologies

Raza, Muhammad Zawwad; Allegrini, Simone; Dumontet, Charles; Jordheim, Lars Petter

doi:10.1002/gcc.22514

Cited by 8 publications

(9 citation statements)

References 81 publications

(176 reference statements)

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“…Accordingly, NMDAR blockade in developing rodent brain leads to apoptotic neuronal death 62,63 . In addition, Kidins220 is important for cellular survival but also for proliferation (reviewed in reference 64 ). Thus, degradation of Kidins220/Rap1/ERK activation complexes in neurons identified herein could also contribute to stop pro-cell division signals triggered through NMDARs during excitotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Excitotoxic targeting of Kidins220 to the Golgi apparatus precedes calpain cleavage of Rap1-activation complexes

et al. 2019

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Excitotoxic neuronal death induced by high concentrations of glutamate is a pathological event common to multiple acute or chronic neurodegenerative diseases. Excitotoxicity is mediated through overactivation of the N-Methyl-D-aspartate type of ionotropic glutamate receptors (NMDARs). Physiological stimulation of NMDARs triggers their endocytosis from the neuronal surface, inducing synaptic activity and survival. However almost nothing is known about the internalization of overactivated NMDARs and their interacting proteins, and how this endocytic process is connected with neuronal death has been poorly explored. Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a component of NMDAR complexes essential for neuronal viability by the control of ERK activation. Here we have investigated Kidins220 endocytosis induced by NMDAR overstimulation and the participation of this internalization step in the molecular mechanisms of excitotoxicity. We show that excitotoxicity induces Kidins220 and GluN1 traffic to the Golgi apparatus (GA) before Kidins220 is degraded by the protease calpain. We also find that excitotoxicity triggers an early activation of Rap1-GTPase followed by its inactivation. Kidins220 excitotoxic endocytosis and subsequent calpain-mediated downregulation governs this late inactivation of Rap1 that is associated to decreases in ERK activity preceding neuronal death. Furthermore, we identify the molecular mechanisms involved in the excitotoxic shutoff of Kidins220/Rap1/ERK prosurvival cascade that depends on calpain processing of Rap1-activation complexes. Our data fit in a model where Kidins220 targeting to the GA during early excitotoxicity would facilitate Rap1 activation and subsequent stimulation of ERK. At later times, activation of Golgi-associated calpain, would promote the degradation of GA-targeted Kidins220 and two additional components of the specific Rap1 activation complex, PDZ-GEF1, and S-SCAM. In this way, late excitotoxicity would turn off Rap1/ERK cascade and compromise neuronal survival.

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Section: Discussionmentioning

confidence: 99%

Excitotoxic targeting of Kidins220 to the Golgi apparatus precedes calpain cleavage of Rap1-activation complexes

et al. 2019

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“…Currently, there is growing evidence showing the involvement of Kidins220/ARMS in various cancers ( Raza et al, 2017 ). As mentioned above, Kidins220/ARMS is a multifunctional transmembrane scaffold protein involved in the regulation of many cellular functions.…”

Section: Roles Of P75 Ntr In Cancer Cell Migrationmentioning

confidence: 99%

From Neural Crest Development to Cancer and Vice Versa: How p75NTR and (Pro)neurotrophins Could Act on Cell Migration and Invasion?

Wislet

Vandervelden

Rogister

2018

Front. Mol. Neurosci.

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The p75 neurotrophin receptor (p75NTR), also known as low-affinity nerve growth factor, belongs to the tumor necrosis factor family of receptors. p75NTR is widely expressed in the nervous system during the development, as well as, in the neural crest population, since p75NTR has been described as ubiquitously expressed and considered as a neural crest marker. Neural crest cells (NCCs) constitute an transient population accurately migrating and invading, with precision, defined sites of the embryo. During migration, NCCs are guided along distinct migratory pathways by specialized molecules present in the extracellular matrix or on the surfaces of those cells. Two main processes direct NCC migration during the development: (1) an epithelial-to-mesenchymal transition and (2) a process known as contact inhibition of locomotion. In adults, p75NTR remains expressed by NCCs and has been identified in an increasing number of cancer cells. Nonetheless, the regulation of the expression of p75NTR and the underlying mechanisms in stem cell biology or cancer cells have not yet been sufficiently addressed. The main objective of this review is therefore to analyze elements of our actual knowledge regarding p75NTR roles during the development (mainly focusing on neural crest development) and see how we can transpose that information from development to cancer (and vice versa) to better understand the link between p75NTR and cell migration and invasion. In this review, we successively analyzed the molecular mechanisms of p75NTR when it interacts with several coreceptors and/or effectors. We then analyzed which signaling pathways are the most activated or linked to NCC migration during the development. Regarding cancer, we analyzed the described molecular pathways underlying cancer cell migration when p75NTR was correlated to cancer cell migration and invasion. From those diverse sources of information, we finally summarized potential molecular mechanisms underlying p75NTR activation in cell migration and invasion that could lead to new research areas to develop new therapeutic protocols.

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“…A growing body of evidence points to a direct role of KIDINS220 in cancer [55-57]. In prostate cancer, KIDINS220 activates the PI3K/AKT pathway [58], and in pediatric high grade glioma copy number breakpoint within KIDINS220 gene have been identified [57].…”

Section: Discussionmentioning

confidence: 99%

Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis

Puerto

Martí-Prado

Barrios-Muñoz

et al. 2023

Preprint

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In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs to proliferate. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair.

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Functions of the multi‐interacting protein KIDINS220/ARMS in cancer and other pathologies

Cited by 8 publications

References 81 publications

Excitotoxic targeting of Kidins220 to the Golgi apparatus precedes calpain cleavage of Rap1-activation complexes

Excitotoxic targeting of Kidins220 to the Golgi apparatus precedes calpain cleavage of Rap1-activation complexes

From Neural Crest Development to Cancer and Vice Versa: How p75NTR and (Pro)neurotrophins Could Act on Cell Migration and Invasion?

Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis

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