Human SLITRK family genes: genomic organization and expression profiling in normal brain and brain tumor tissue

Aruga, Jun; Yokota, Naoki; Mikoshiba, Katsuhiko

doi:10.1016/s0378-1119(03)00715-7

Cited by 126 publications

(125 citation statements)

References 16 publications

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“…Six Slitrk family members (Slitrk1-6) share similar domain organizations and have been shown to regulate neurite outgrowth in Pheochromocytoma Cell Line 12 (PC12) cells (5,28). Intriguingly, various Slitrk-KO mice exhibit a range of neurological behaviors, implying differential functions of these proteins in the CNS (12,29,30).…”

Section: Discussionmentioning

confidence: 99%

Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases

Yim

Kwon

Nam

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

161

217

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The balance between excitatory and inhibitory synaptic inputs, which is governed by multiple synapse organizers, controls neural circuit functions and behaviors. Slit-and Trk-like proteins (Slitrks) are a family of synapse organizers, whose emerging synaptic roles are incompletely understood. Here, we report that Slitrks are enriched in postsynaptic densities in rat brains. Overexpression of Slitrks promoted synapse formation, whereas RNAi-mediated knockdown of Slitrks decreased synapse density. Intriguingly, Slitrks were required for both excitatory and inhibitory synapse formation in an isoform-dependent manner. Moreover, Slitrks required distinct members of the leukocyte antigen-related receptor protein tyrosine phosphatase (LAR-RPTP) family to trigger synapse formation. Protein tyrosine phosphatase σ (PTPσ), in particular, was specifically required for excitatory synaptic differentiation by Slitrks, whereas PTPδ was necessary for inhibitory synapse differentiation. Taken together, these data suggest that combinatorial interactions of Slitrks with LAR-RPTP family members maintain synapse formation to coordinate excitatory-inhibitory balance.leucine-rich repeat | neuropsychiatic disorder | synaptic cell-adhesion

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Section: Discussionmentioning

confidence: 99%

Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases

Yim

Kwon

Nam

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

161

217

View full text Add to dashboard Cite

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“…1 An important feature is that most normal human B-cells exiting the GC express and retain CD27 in the periphery. 2 Waldenstrom's macroglobulinemia (WM) is a distinct clinicopathological entity with an underlying monoclonal IgM lymphoplasmacytic lymphoma. It locates primarily in the bone marrow (BM) as a tumor of mature sIgM þ ve B-cells, some maturing to secrete immunoglobulin.…”

Section: Igm-expressing Waldenstrom's Macroglobulinemia Tumor Cells Rmentioning

confidence: 99%

“…1 Slitrks are highly conserved through evolution, with the human slitrks being 89-97% homologous to murine slitrks. 2 Aruga and Mikoshiba 1 described the expression pattern of these genes in the developing brain and spinal cord, as well as their involvement in controlling neurite migration and axonal guidance. We described previously the differential expression of slitrk5 (referred to as KIAA0918) on CD34 þ leukemic cell lines.…”

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confidence: 99%

A novel family of slitrk genes is expressed on hematopoietic stem cells and leukemias

et al. 2007

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In summary, this study confirms that TMZ has activity in AML, and indicates that anti-leukemic responses correlate with MGMT expression, particularly in previously untreated patients. This correlation supports in vitro data indicating that MGMT is an important mediator of leukemia cell resistance to this agent. These findings require validation in a follow-up study, and such a study is currently in progress. If confirmed, this would establish TMZ as a reasonable front-line therapy option for older AML patients who are poor candidates for conventional induction chemotherapy, and whose blasts demonstrate very low or absent MGMT expression. Furthermore, MGMT-negative AML may potentially be a useful target for TMZ-containing combination regimens.

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“…1,2 Structurally, Slitrk proteins share leucinerich repeat (LRR) domains located N terminus to the transmembrane domain. LRR domains are present in many proteins and mediate protein-protein interactions.…”

Section: Introductionmentioning

confidence: 99%

“…5 The C-terminal domain is conserved in all Slitrk proteins except Slitrk1. 1,2 Several type I transmembrane proteins with LRR domains have been identified till date, and most are produced predominantly in the nervous system. 6 In addition to LRR domains, many type I transmembrane proteins have motifs typical of cell adhesion molecules, such as immunoglobulin-like and fibronectin type III domains.…”

Section: Introductionmentioning

confidence: 99%

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities

et al. 2008

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Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an a2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plusmaze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

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Human SLITRK family genes: genomic organization and expression profiling in normal brain and brain tumor tissue

Cited by 126 publications

References 16 publications

Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases

Slitrks control excitatory and inhibitory synapse formation with LAR receptor protein tyrosine phosphatases

A novel family of slitrk genes is expressed on hematopoietic stem cells and leukemias

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities

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