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Last update 08 May 2025

ASTN2

Last update 08 May 2025

Basic Info

Synonyms

ASTN2, astrotactin 2, Astrotactin-2

+ [1]

Introduction

Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons. Promotes ASTN1 internalization and intracellular transport of endocytosed ASTN1 (By similarity). Selectively binds inositol-4,5-bisphosphate, inositol-3,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, suggesting it is recruited to membranes that contain lipids with a phosphoinositide headgroup (Ref.6).

Drugs associated with ASTN2

DEX A-P Vaccine(Jinan University)

Target

ASTN2 x PAPPA1

Mechanism

ASTN2 modulators [+1]

Active Org.

Jinan University

Originator Org.

Jinan University

Active Indication

Esophageal Carcinoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ASTN2

100 Translational Medicine associated with ASTN2

0 Patents (Medical) associated with ASTN2

Literatures (Medical) associated with ASTN2

20 Aug 2024·Proceedings of the National Academy of Sciences

Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties

Article

Author: Hull, Court ; Fernando, Kayla ; Maloney, Susan E. ; Zhao, Jiajia ; Hanzel, Michalina ; Mätlik, Kärt ; Pasolli, H. Amalia ; Dougherty, Joseph D. ; Hatten, Mary E. ; Horn, Zachi ; Heissel, Søren ; Gong, Shiaoching

Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with ASTN2 mutations exhibit neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional Astn2 knockout (KO and cKO, respectively) mouse lines. Astn2 KO mice exhibit strong ASD-related behavioral phenotypes, including a marked decrease in separation-induced pup ultrasonic vocalization calls, hyperactivity, repetitive behaviors, altered behavior in the three-chamber test, and impaired cerebellar-dependent eyeblink conditioning. Hyperactivity and repetitive behaviors are also prominent in Astn2 cKO animals, but they do not show altered behavior in the three-chamber test. By Golgi staining, Astn2 KO PCs have region-specific changes in dendritic spine density and filopodia numbers. Proteomic analysis of Astn2 KO cerebellum reveals a marked upregulation of ASTN2 family member, ASTN1, a neuron–glial adhesion protein. Immunohistochemistry and electron microscopy demonstrate a significant increase in Bergmann glia volume in the molecular layer of Astn2 KO animals. Electrophysiological experiments indicate a reduced frequency of spontaneous excitatory postsynaptic currents (EPSCs), as well as increased amplitudes of both spontaneous EPSCs and inhibitory postsynaptic currents in the Astn2 KO animals, suggesting that pre- and postsynaptic components of synaptic transmission are altered. Thus, ASTN2 regulates ASD-like behaviors and cerebellar circuit properties.

01 May 2024·Environmental Toxicology

Similar toxicity potential of glyphosate and glyphosate‐based herbicide on cerebellar development after maternal exposure in rats

Article

Author: Shibutani, Makoto ; Ozawa, Shunsuke ; Zou, Xinyu ; Ojiro, Ryota ; Tang, Qian ; Woo, Gye‐Hyeong

AbstractStudies on the effects of glyphosate (GlyP) and glyphosate‐based herbicides (GBHs) on cerebellar development are extremely limited. This study examined the effects of maternal exposure to GlyP and GBH on rat cerebellar development in male offspring. From day 6 of gestation until day 21 postpartum at weaning, dams were given GlyP at 1.5% or 3.0% in diet or GBH at 1.0% in drinking water (corresponding to 0.36% GlyP). At weaning, GBH exposure was linked to increased numbers of DCX+ migrating granule cells in the cortex and TUNEL+ apoptotic cells in the internal granular layer (IGL), suggesting the disappearance of mismigrated granule cells via apoptosis. GBH also upregulated Nr4a3 and downregulated Cdk5 in the cerebellar vermis, suggesting a causal relation with the impaired granule cell development at this time. GlyP (3.0%) tended to increase in the number of DCX+ migrating granule cells in the IGL and upregulated Nr4a3 at weaning. Both compounds also upregulated genes related to granule cell migration (Astn1, Astn2, Nfia, and/or Nfix) at weaning and in adulthood, which might be an ameliorative response to delayed granule cell migration. Moreover, GBH induced Purkinje cell misalignment at weaning, which could be the result of delayed granule cell migration. In adulthood, GBH was associated with upregulation of the reelin signaling‐related genes Reln, Dab1, and Efnb1, suggesting a compensatory response to Purkinje cell misalignment. GlyP induced the same gene expression changes. These results suggest that GBH reversibly disrupts cerebellar development, primarily by targeting granule cell migration and differentiation, whereas GlyP exhibited similar toxic potential as GBH.

01 Jan 2024·Frontiers in genetics

Genome-wide associations with longevity and reproductive traits in U.S. rangeland ewes

Article

Author: Becker, Gabrielle M ; Taylor, J Bret ; Schaub, Daniel ; Murdoch, Brenda M ; Thorne, Jacob W ; Smitchger, Jamin A ; Mousel, Michelle R

Introduction: Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait. Characterizing genetic factors underpinning ewe longevity and related traits could result in the development of genomic selection strategies to improve the stayability of sheep through early, informed selection of replacement ewes. Methods: Towards this aim, a genome-wide association study (GWAS) was performed to identify genetic markers associated with ewe longevity, reproductive, and production traits. Traits evaluated included longevity (i.e., length of time in the flock), parity and the lifetime number of lambs born, lambs born alive, lambs weaned, and weight of lambs weaned. Ewe records from previous studies were used. Specifically, Rambouillet (n = 480), Polypay (n = 404), Suffolk (n = 182), and Columbia (n = 64) breed ewes (N = 1,130) were analyzed against 503,617 SNPs in across-breed and within-breed GWAS conducted with the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model in R. Results: The across-breed GWAS identified 25 significant SNPs and the within-breed GWAS for Rambouillet, Polypay, and Suffolk ewes identified an additional 19 significant SNPs. The most significant markers were rs411309094 (13:22,467,143) associated with longevity in across-breed GWAS (p-value = 8.3E-13) and rs429525276 (2:148,398,336) associated with both longevity (p-value = 6.4E-15) and parity (p-value = 4.8E-15) in Rambouillet GWAS. Significant SNPs were identified within or in proximity (±50 kb) of genes with known or proposed roles in reproduction, dentition, and the immune system. These genes include ALPL, ANOS1, ARHGEF26, ASIC2, ASTN2, ATP8A2, CAMK2D, CEP89, DISC1, ITGB6, KCNH8, MBNL3, MINDY4, MTSS1, PLEKHA7, PRIM2, RNF43, ROBO2, SLCO1A2, TMEM266, TNFRSF21, and ZNF804B. Discussion: This study proposes multiple SNPs as candidates for use in selection indices and suggests genes for further research towards improving understanding of the genetic factors contributing to longevity, reproductive, and production traits of ewes.

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ASTN2

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