Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5

Kodani, Andrew; Kenny, Connor; Lai, Abbe; Gonzalez, Dilenny M.; Stronge, Edward; Sejourne, Gabrielle M.; Isacco, Laura; Partlow, Jennifer N.; O’Donnell, Anne H.; McWalter, Kirsty; Byrne, Alicia B.; Barkovich, A. James; Yang, Edward; Hill, Robert S.; Gawliński, Paweł; Wiszniewski, Wojciech; Cohen, Julie S.; Fatemi, Seyed Ali; Barañano, Kristin W.; Şahin, Mustafa; Vossler, David G.; Yuskaitis, Christopher J.; Walsh, Christopher A.

doi:10.1016/j.neuron.2020.01.030

Cited by 20 publications

(26 citation statements)

References 45 publications

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“…Nuclear-centrosomal coordination is important for cell movement. found to be more strongly expressed in human visual than in frontal cortex [29 ] which might help explain the milder or unaffected frontal lobes. With KD by IUE in the mouse, Cep85l-depleted cells were found blocked in the IZ [28,29 ].…”

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 93%

“…found to be more strongly expressed in human visual than in frontal cortex [29 ] which might help explain the milder or unaffected frontal lobes. With KD by IUE in the mouse, Cep85l-depleted cells were found blocked in the IZ [28,29 ]. In scratch-wound migration assays, cells were found to correctly orient their centrosomes, however, impaired MT dynamics were identified surrounding the centrosome with an overabundance of newly-synthesized MTs [29 ].…”

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 93%

“…Patients were identified with rare heterozygous variants in CEP85L, coding for a centrosome-associated protein located to the mother centriole [28,29 ]. Mutations give rise to an agyria, pachygyria-SBH spectrum, most severe over occipital, temporal and parietal lobes.…”

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 99%

“…With KD by IUE in the mouse, Cep85l-depleted cells were found blocked in the IZ [28,29 ]. In scratch-wound migration assays, cells were found to correctly orient their centrosomes, however, impaired MT dynamics were identified surrounding the centrosome with an overabundance of newly-synthesized MTs [29 ]. CEP85L was shown to interact with LIS1, NDE1, KIF2A, DYNC1H1 and CDK5 [29 ], with CDK5 activity necessary to restrict the centrosomal accumulation of these lissencephaly proteins.…”

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 99%

See 3 more Smart Citations

Neuronal migration and disorders – an update

Francis

Cappello

2021

Current Opinion in Neurobiology

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Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 93%

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 93%

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 99%

Section: Mt Dynamics and Function In Migrating Neuronsmentioning

confidence: 99%

See 2 more Smart Citations

Neuronal migration and disorders – an update

Francis

Cappello

2021

Current Opinion in Neurobiology

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“…CDK5 was an already well-known regulator of neuronal cytoskeleton dynamics, directly or indirectly engaging some of these 20 proteins (reviewed in [76]). The recent discovery of a new lissencephalic syndrome caused by mutations in CEP85L allowed to unveil an important interaction with CDK5, which drives the localization and activation of the kinase at the centrosome to ensure proper organization of centrosome and cytoskeleton [77] (Fig. 1).…”

Section: Human Genetics Looms Cdk/cyclin Regulatory Networkmentioning

confidence: 99%

Cyclin-dependent kinases and rare developmental disorders

Colas

2020

Orphanet J Rare Dis

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Extensive studies in the past 30 years have established that cyclin-dependent kinases (CDKs) exert many diverse, important functions in a number of molecular and cellular processes that are at play during development. Not surprisingly, mutations affecting CDKs or their activating cyclin subunits have been involved in a variety of rare human developmental disorders. These recent findings are reviewed herein, giving a particular attention to the discovered mutations and their demonstrated or hypothesized functional consequences, which can account for pathological human phenotypes. The review highlights novel, important CDK or cyclin functions that were unveiled by their association with human disorders, and it discusses the shortcomings of mouse models to reveal some of these functions. It explains how human genetics can be used in combination with proteome-scale interaction databases to loom regulatory networks around CDKs and cyclins. Finally, it advocates the use of these networks to profile pathogenic CDK or cyclin variants, in order to gain knowledge on protein function and on pathogenic mechanisms.

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Further characterization of CEP85L‐associated lissencephaly type 10: Report of a three‐generation family and review of the literature

Leduc‐Pessah,

White‐Brown,

Miller

et al. 2023

American J of Med Genetics Pt A

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Lissencephaly type 10 is a recently reported condition characterized by posterior predominant abnormalities in gyration with associated seizures, developmental delays or intellectual disability. We report a boy who presented at 5 years of age with epilepsy and developmental delays. His family history was notable for epilepsy in two prior generations associated with variable developmental and cognitive impact. Exome sequencing identified a novel missense variant in CEP85L [NM_001042475.2; c.196A>G, p.(Thr66Ala)] which segregated in four affected family members across three generations. Brain imaging of the proband demonstrated a posterior lissencephaly pattern with pachygyria, while other affected family members demonstrated a similar subcortical band heterotopia. This report expands the phenotypic spectrum of this rare disorder by describing a novel variant in CEP85L in a family with variable clinical and neuroimaging findings.

show abstract

Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5

Abstract: Highlights d Mutations in CEP85L cause posterior-specific pachygyria d CEP85L is required for neuronal migration d Loss of CEP85L disrupts centrosome organization and function d CEP85L localizes and activates CDK5 at the centrosome

Cited by 20 publications

References 45 publications

Neuronal migration and disorders – an update

Neuronal migration and disorders – an update

Cyclin-dependent kinases and rare developmental disorders

Further characterization of CEP85L‐associated lissencephaly type 10: Report of a three‐generation family and review of the literature

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