The Role of SliTrk5 in Central Nervous System

Abstract

SLIT and NTRK-like protein-5 (SliTrk5) is one of the six members of SliTrk protein family, which is widely expressed in the central nervous system (CNS), regulating and participating in many essential steps of central nervous system development, including axon and dendritic growth, neuron differentiation, and synaptogenesis. SliTrk5, as a neuron transmembrane protein, contains two important conservative domains consisting of leucine repeats (LRRs) located at the amino terminal in the extracellular region and tyrosine residues (Tyr) located at the carboxyl terminal in the intracellular domains. These special structures make SliTrk5 play an important role in the pathological process of the CNS. A large number of studies have shown that SliTrk5 may be involved in the pathogenesis of CNS diseases, such as obsessive-compulsive-disorder (OCD), attention deficit/hyperactivity disorder (ADHD), glioma, autism spectrum disorders (ASDs), and Parkinson’s disease (PD). Targeting SliTrk5 is expected to become a new target for the treatment of CNS diseases, promoting the functional recovery of CNS. The purpose of this article is to review the current research progression of the role of SliTrk5 in CNS and its potential mechanisms in CNS diseases.

A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth

“…Other notable proteins among the 37 positively associated with LAZ include insulin-like growth factor-1 (IGF-1) which acts in concert with growth hormone to control linear growth in children 46 and a Wnt inhibitor, secreted frizzled-related protein 4 (SFRP4), involved in formation of bone cortex 47 . The list also includes effectors of CNS development: e.g., RET which encodes the receptor tyrosine kinase for glial cell derived neurotrophic factor (GDNF) 48 ; the axon guidance protein SLIT and NTRK like family member 5 (SLITRK5) 49 , BDNF/NT-3 growth factors receptor (NTRK2) which is involved in synaptogenesis and learning and memory 50 , plus roundabout homolog 2 (ROBO2), an axon guidance receptor recently reported to also promote osteoblast differentiation and mineralization 51 (see Fig. 3b for complete list of these proteins and their functional annotations).…”

“…The list also includes effectors of CNS development: e.g., RET which encodes the receptor tyrosine kinase for glial cell derived neurotrophic factor (GDNF) 48 ; the axon guidance protein SLIT and NTRK like family member 5 (SLITRK5) 49 , BDNF/NT-3 growth factors receptor (NTRK2) which is involved in synaptogenesis and learning and memory 50 , plus roundabout homolog 2 (ROBO2), an axon guidance receptor recently reported to also promote osteoblast differentiation and mineralization 51 (see Fig. 3b for complete list of these proteins and their functional annotations).…”

A microbiota-directed complementary food intervention in 12–18-month-old Bangladeshi children improves linear growth

“…Other notable proteins among the 37 positively associated with LAZ include insulin-like growth factor-1 (IGF-1) which acts in concert with growth hormone to control linear growth in children 46 and a Wnt inhibitor, secreted frizzled-related protein 4 (SFRP4), involved in formation of bone cortex. 47 The list also includes effectors of CNS development: e.g., RET which encodes the receptor tyrosine kinase for glial cell derived neurotrophic factor (GDNF) 48 ; the axon guidance protein SLIT and NTRK like family member 5 (SLITRK5), 49 BDNF/NT-3 growth factors receptor (NTRK2) which is involved in synaptogenesis and learning and memory, 50 plus roundabout homolog 2 (ROBO2), an axon guidance receptor recently reported to also promote osteoblast differentiation and mineralization 51 (see Fig. 3 b for complete list of these proteins and their functional annotations).…”

Upregulation of SLITRK5 in patients with epilepsy and in a rat model

“…SLITRK5 was generally expressed in the developing central nervous system at times and locations that are important to neuronal morphogenesis and synaptogenesis (Beaubien & Cloutier, 2009;Round et al, 2014), as well as in embryonic stem cells, subsets of endothelial cells, hematopoietic stem cells, and in leukemia and lymphoma cells . SLITRK5 is associated with many neurological disorders (Liu et al, 2022), which can be combined with the synaptic adhesion molecules (SAMs), type IIa receptor protein tyrosine phosphatase (RPTP), controlling synapse formation, thus regulating the connections between neurons (Beaubien et al, 2016;O'Sullivan et al, 2012;Shmelkov et al, 2001;Song et al, 2015).Additionally, SLITRK5 is associated with a variety of tumors, such as brain glioma, thyroid tumors, gastric cancer, nasopharyngeal carcinoma, lung squamous cell carcinoma, and colorectal tumor (Haoran & Yanhua, 2018;Heiliger et al, 2012;Hesson et al, 2016;Ju et al, 2020;Li et al, 2016;Park et al, 2016). Beyond that, SLITRK5 can negatively regulate dendritic growth, controlling the inhibitory synapse formation on dopamine neurons and modulating hyperactivity behavior (Salesse et al, 2020).…”