Functional analysis of the CNS-specific F-box protein FBXO41 in cerebellar development

Mukherjee, Chaitali

dc.contributor.advisor	Stegmüller, Judith Dr.
dc.contributor.author	Mukherjee, Chaitali
dc.date.accessioned	2015-10-16T09:29:26Z
dc.date.available	2015-10-16T09:29:26Z
dc.date.issued	2015-10-16
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0023-9648-1
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-5309
dc.language.iso	eng	de
dc.relation.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	Functional analysis of the CNS-specific F-box protein FBXO41 in cerebellar development	de
dc.type	doctoralThesis	de
dc.title.translated	Functional analysis of the CNS-specific F-box protein FBXO41 in cerebellar development	de
dc.contributor.referee	Stegmüller, Judith Dr.
dc.date.examination	2015-06-08
dc.description.abstracteng	Neurodevelopment is a highly dynamic process governed by the tight orchestration of events such as neurogenesis, neuronal migration, morphogenesis and synaptogenesis that ultimately shape the brain. These neurodevelopmental events are tightly regulated by the interplay of cell-extrinsic and intrinsic mechanisms. Over the past decades, the ubiquitin proteasome system has emerged as an intrinsic regulator of neurodevelopment as well as disease. In this study, I explored the function of the CNS-specific F-box protein FBXO41 in vivo and established it as a key regulator of cerebellar development. I found that loss of FBXO41 results in a severely ataxic and uncoordinated gait in mice, along with impaired granule neuron migration, neurodegeneration and axon growth defects in the cerebellum. In addition, I identified FBXO41 as the second F-box protein to form an SCF-like E3 ligase complex with cullin7. Furthermore, I discovered that FBXO41-Cul7 non-proteolytically ubiquitinates the cytoskeletal protein neurofilament medium polypeptide (NFM), thereby stabilizing it. Last but not the least, I uncovered that FBXO41-Cul7 operates upstream of NFM in the pathway of axon growth regulation. Collectively, my study has uncovered the function of FBXO41 in cerebellar development and has identified FBXO41-Cul7 as a novel E3 ligase providing the first insights into its ligase activity and axon growth regulation.	de
dc.contributor.coReferee	Simons, Mikael Prof. Dr.
dc.subject.eng	Ataxia	de
dc.subject.eng	Axon growth	de
dc.subject.eng	Cerebellum	de
dc.subject.eng	Cullin7	de
dc.subject.eng	neuronal migration	de
dc.subject.eng	neurofilament	de
dc.subject.eng	FBXO41	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0023-9648-1-5
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	837421403

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1015]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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