Neuronal distribution of Spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17

Irla, Magali; Saade, Murielle; Fernandez, Carla; Chasson, Lionel; Victoréro, Geneviève; Dahmane, Nadia; Chazal, Geneviève; Nguyen, Catherine

doi:10.1016/j.yexcr.2007.09.006

Cited by 10 publications

(17 citation statements)

References 26 publications

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“…Dendrites and flagella share similar microtubule-based motor proteins essential for vesicle migration and positioning [12]. According to the highly specific distribution of Spatial in cellular extensions, we determined its association to the kinesin motor KIF17 conserved in the flagellum and dendrites [10,11]. These previous findings thus imply a function of Spatial in cell differentiation in a microtubule-dependent mechanism.…”

Section: Introductionmentioning

confidence: 78%

“…According to the size of alternative spliced variants, we have respectively named Spatial isoforms: Spatial-a (1035 bp), Spatial-b (1002 bp), Spatial-g (933 bp) for the short isoforms identified in the thymus; Spatial-d (1353 bp) and Spatial-e (1454 bp) for the long isoforms identified in the testis [8]. In addition, we have recently identified its expression in the CNS, more particularly in the cerebellum and the hippocampus in which only Spatial-e and -b isoforms are expressed [11].The characterization of Spatial in the testis showed that during spermiogenesis, Spatial proteins are polarized in the nascent flagellum and in the manchette during spermatids morphogenesis [10]. In the CNS, Spatial expression tightly overlaps with the beginning of neuronal differentiation exhibiting a somatodendritic distribution in adult neurons [11].…”

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confidence: 99%

“…In addition, we have recently identified its expression in the CNS, more particularly in the cerebellum and the hippocampus in which only Spatial-e and -b isoforms are expressed [11].…”

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confidence: 99%

“…Spatial expression was detected at E10.5. and E11.5 in all pharyngeal regions as well as in the CNS [11], suggesting that this gene could have a key role during embryonic development. In the third pharyngeal pouch endoderm that is fated to develop into thymus and parathyroid, Spatial expression pattern was compared with Foxn1 by ISH analysis at E11.5 (Supporting Information data 1) [14].…”

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confidence: 99%

“…Surprisingly, Spatial long isoforms were also detected in the same TEC populations. Since Spatial long isoforms are expressed in peripheral tissues, such as the brain and testis [10,11], we can suggest that their expression in mature mTEC could be ectopic as promiscuously expressed genes (also known as TRA) involved in the prevention of autoimmune disease by a mechanism known as central tolerance [27].We further immunophenotyped Spatial expression in mature mTEC by co-staining analyses with the lectin UEA1 and Aire on thymus sections (Fig. 2C).…”

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confidence: 99%

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Spatial (Tbata) expression in mature medullary thymic epithelial cells

et al. 2010

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The Spatial gene is expressed in highly polarized cell types such as testis germ cells, brain neurons and thymic epithelial cells (TEC). Its expression was documented in testis and brain but poorly characterized in thymus. Here, we characterize for the first time Spatial-expressing TEC throughout ontogeny and adult mouse thymus. Spatial is expressed in thymicfated domain by embryonic day E10.5 and persists in subcapsular, cortical, medullary epithelial cells and in MTS24 1 progenitor TEC. Using mouse strains in which thymocyte development is blocked at various stages, we show that Spatial expression is independent of thymocyte-derived signals during thymus organogenesis. Analyses on purified thymic cell subsets show that Spatial short isoforms are expressed in cortical TEC (cTEC) and mature medullary TEC (mTEC). Spatial long isoforms were detected in the same TEC population. Spatial presents a nuclear distribution specific to mature mTEC expressing UEA1 and Aire. Aire-and RANKL-deficient mice revealed that Spatial expression is drastically reduced in the thymus of these mutants. These findings reveal a critical function of Aire in regulating Spatial expression, which is compatible with promiscuous Spatial gene expression. 530 IntroductionThe vertebrate thymus is responsible for the production of functional nonautoreactive T lymphocytes. In this primary lymphoid organ, T-cell precursors commonly called thymocytes undergo a series of developmental stages through interactions with thymic stromal cells, resulting in the generation of mature T lymphocytes that are exported to the periphery [1,2]. The unique function of the thymus resides mainly in the thymic epithelium, which forms the major subcompartment of the stroma [3,4]. The thymic epithelium itself is commonly divided into two main regions, the cortex and the medulla, and each of these regions contains several ultrastructurally and phenotypically distinct types of thymic epithelial cells (TEC) [5,6]. TEC are required both for thymus organogenesis and for the promotion of most if not all stages of thymocyte maturation [3,4]. Understanding the molecular mechanisms regulating TEC differentiation and function provides crucial insights into mechanisms controlling T-cell development in the thymus.Using DNA chip technology we isolated the Spatial gene (Stromal Protein Associated with Thymii and Lymph node), also known as Tbata (thymus, brain and testes associated), by an approach based on differential screening between different knock-out mice models exhibiting distinct thymic immunodeficiencies [7]. This analysis led to the identification of three adult variants of the Spatial gene expressed in the thymus [8]. In addition, we also described two other isoforms isolated in the testis [8][9][10]. According to the size of alternative spliced variants, we have respectively named Spatial isoforms: Spatial-a (1035 bp), Spatial-b (1002 bp), Spatial-g (933 bp) for the short isoforms identified in the thymus; Spatial-d (1353 bp) and Spatial-e (1454 bp) for the long isoforms ...

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Section: Introductionmentioning

confidence: 78%

mentioning

confidence: 99%

“…In addition, we have recently identified its expression in the CNS, more particularly in the cerebellum and the hippocampus in which only Spatial-e and -b isoforms are expressed [11].…”

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Spatial (Tbata) expression in mature medullary thymic epithelial cells

et al. 2010

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Three-Step Model for Polarized Sorting of KIF17 into Dendrites

et al. 2016

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Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11]. Using live-cell imaging combined with inducible trafficking assays to directly probe KIF17 motor activity in living neurons, we found that the polarized sorting of KIF17 to dendrites is regulated in multiple steps. First, cargo binding of KIF17 relieves autoinhibition and initiates microtubule-based cargo transport. Second, KIF17 does not autonomously target dendrites, but enters the axon where the actin cytoskeleton at the axon initial segment (AIS) prevents KIF17 vesicles from moving further into the axon. Third, dynein-based motor activity is able to redirect KIF17-coupled cargoes into dendrites. We propose a three-step model for polarized targeting of KIF17, in which the collective function of multiple motor teams is required for proper dendritic sorting.

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