Fbxo45 Inhibits Calcium-sensitive Proteolysis of N-cadherin and Promotes Neuronal Differentiation

Chung, Fu Zon; Sahasrabuddhe, Anagh A.; Ma, Kaiyu; Chen, Xiaofei; Basrur, Venkatesha; Lim, Megan S.; Elenitoba-Johnson, Kojo S.J.

doi:10.1074/jbc.m114.561241

Cited by 21 publications

(24 citation statements)

References 39 publications

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“…We did not observe coprecipitation of HA-SKP1 with any GFP-PAM fragments (Fig 4C). Consistent with prior work (37,57), HA-SKP1 did coIP with GFP-FBXO45 (Fig. 4C).…”

Section: Fbxo45 Recruits Skp1 Into a Complex With Pamsupporting

confidence: 80%

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PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2

Desbois

Crawley

Evans

et al. 2018

Journal of Biological Chemistry

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“…We did not observe coprecipitation of HA-SKP1 with any GFP-PAM fragments (Fig 4C). Consistent with prior work (37,57), HA-SKP1 did coIP with GFP-FBXO45 (Fig. 4C).…”

Section: Fbxo45 Recruits Skp1 Into a Complex With Pamsupporting

confidence: 80%

“…Previous biochemical and proteomic experiments using cultured cells showed SKP1 binds to FBXO45 (37,57). Affinity purification proteomics with Highwire in flies also identified the SKP1 ortholog, SkpA (40).…”

Section: Fbxo45 Recruits Skp1 Into a Complex With Pammentioning

confidence: 96%

PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2

Desbois

Crawley

Evans

et al. 2018

Journal of Biological Chemistry

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“…On the other hand, the binding of SKP1 to FBXO45 is known to involve the F-box domain [36] and therefore FBXO45 is well suited to support the unhindered indirect interaction of Hey1 and SKP1, which was supported by experimental evidence. Our data are also in full agreement with recent analyses of Fbxo45 interactors in U87MG cells that found SPRY domain / PAM and F-box / Skp1 interactions [37]. We could not find the interaction of Fbxo45 with the extracellular domain of N-cadherin described in that publication, but this may be due to differences in subcellular localization.…”

Section: Discussionsupporting

confidence: 93%

Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus

Salat

Winkler

Urlaub³

et al. 2015

PLoS ONE

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The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors.

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“…Taken together, our data suggest that the NCad but not ECad EC1-2 domains are necessary and sufficient to bind Fbxo45. This finding is consistent with our observation that Fbxo45 was more efficiently biotinylated if BirA* was fused into EC2 than into the juxtamembrane region (compare N2-BirA* and N5-BirA*, Table 1), and with a previous report (32).…”

Section: The Ec1-2 Region Of Ncad Interacts With the Spry Domain Of Fsupporting

confidence: 93%

“…The SPRY domain of Fbxo45 potentially interacts with substrates. Curiously, NCad was detected in a Fbxo45 interaction screen (32). Furthermore, knockdown of Fbxo45 decreased NCad expression and impaired differentiation of neuronal stem cells (32), suggesting that Fbxo45 interaction with NCad is involved in brain development.…”

Section: Introductionmentioning

confidence: 99%

Fbxo45 binds SPRY motifs in the extracellular domain of N-cadherin and regulates neuron migration during brain development

Jiménez

Kon

et al. 2019

Preprint

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ABSTRACTSeveral events during normal development of the mammalian neocortex depend on N-cadherin, including the radial migration of immature projection neurons into the cortical plate. Remarkably, radial migration requires the N-cadherin extracellular domain but not N-cadherin-dependent homophilic cell-cell adhesion, suggesting that other N-cadherin-binding proteins may be involved. We used proximity ligation and affinity purification proteomics to identify N-cadherin-binding proteins. Both screens detected MycBP2 and SPRY-domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. Fbxo45 appears to be secreted by a non-classical mechanism, not involving a signal peptide and not requiring endoplasmic reticulum to Golgi transport. Fbxo45 binding requires N-cadherin SPRY motifs that are not involved in cell-cell adhesion. SPRY-mutant N-cadherin does not support radial migration in vivo. Radial migration was similarly inhibited when Fbxo45 expression was suppressed. The results suggest that projection neuron migration requires both Fbxo45 and binding of Fbxo45 or another protein to SPRY motifs in the extracellular domain of N-cadherin.

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Fbxo45 Inhibits Calcium-sensitive Proteolysis of N-cadherin and Promotes Neuronal Differentiation

Cited by 21 publications

References 39 publications

PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2

PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2

Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus

Fbxo45 binds SPRY motifs in the extracellular domain of N-cadherin and regulates neuron migration during brain development

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