STK38L

Last update 08 May 2025

Basic Info

Synonyms

KIAA0965, NDR2, NDR2 protein kinase

+ [5]

Introduction

Involved in the regulation of structural processes in differentiating and mature neuronal cells.

100 Clinical Results associated with STK38L

100 Translational Medicine associated with STK38L

0 Patents (Medical) associated with STK38L

101

Literatures (Medical) associated with STK38L

15 Jan 2025·Journal of Cell Science

Rabin8 phosphorylated by NDR2, the canine early retinal degeneration gene product, directs rhodopsin Golgi-to-cilia trafficking

Article

Author: Moritz, Orson L. ; Tam, Beatrice M. ; Deretic, Dusanka ; Fresquez, Theresa ; Robichaux, Michael A. ; Eshelman, Shannon C.

ABSTRACTThe Rab11–Rabin8–Rab8 ciliogenesis complex regulates the expansion of cilia-derived light-sensing organelles, the rod outer segments, via post-Golgi rhodopsin transport carriers (RTCs). Rabin8 (also known as RAB3IP), an effector of Rab11 proteins and a nucleotide exchange factor (GEF) for Rab8 proteins, is phosphorylated at S272 by NDR2 kinase (also known as STK38L), the canine early retinal degeneration (erd) gene product linked to the human ciliopathy Leber congenital amaurosis (LCA). Here, we define the step at which NDR2 phosphorylates Rabin8 and regulates Rab11-to-Rab8 succession in Xenopus laevis transgenic rod photoreceptors expressing human GFP–Rabin8 and its mutants. GFP–Rabin8 accumulated with endogenous Rabin8 at the Golgi-apposed exit sites (GESs), also known as the trans-Golgi network (TGN). Rabin8 mutants deficient in Rab11 binding prevented membrane association of GFP–Rabin8. GFP–Rabin8 and NDR2 kinase both interacted with the RTC-associated R-SNARE VAMP7 at the trans-Golgi and the GESs. Here, GFP–Rabin8 and the phosphomimetic GFP–Rabin8-S272E integrated into RTCs, which were subsequently functionalized by Rabin8 Rab8 GEF activity. Non-phosphorylatable GFP–Rabin8-S272A caused significant GES enlargement and deformation, possibly leading to unconventional membrane advancement toward the cilium, bypassing RTCs. Rabin8 phosphorylation loss due to an NDR2 gene disruption thereby likely causes dysfunctional rhodopsin Golgi-to-cilia trafficking underlying retinal degeneration and early-onset blindness.

09 Jan 2025·JCI Insight

NDR2 is critical for osteoclastogenesis by regulating ULK1-mediated mitophagy

Article

Author: Zhao, Fengdong ; Huang, Bao ; Shan, Zhi ; Ji, Zhongyin ; Wang, Xiao-Jian ; Tao, Siyue ; Chen, Jian ; Liu, Junhui ; Lin, Wenlong ; Zhao, Yihao ; Wang, Jian ; Kong, Xiangxi ; Jin, Jiayan ; Chen, Jingyun

Bone homeostasis primarily stems from the balance between osteoblasts and osteoclasts, wherein an augmented number or heightened activity of osteoclasts is a prevalent etiological factor in the development of bone loss. Nuclear Dbf2-related kinase (NDR2), also known as STK38L, is a member of the Hippo family with serine/threonine kinase activity. We unveiled an upregulation of NDR2 expression during osteoclast differentiation. Manipulation of NDR2 levels through knockdown or overexpression facilitated or hindered osteoclast differentiation, respectively, indicating a negative feedback role for NDR2 in the osteoclastogenesis. Myeloid NDR2-dificient mice (Lysm+NDR2fl/fl) showed lower bone mass and further exacerbated ovariectomy-induced or aging-related bone loss. Mechanically, NDR2 enhanced autophagy and mitophagy through mediating ULK1 instability. In addition, ULK1 inhibitor (ULK1-IN2) ameliorated NDR2 conditional KO-induced bone loss. Finally, we clarified a significant inverse association between NDR2 expression and the occurrence of osteoporosis in patients. The NDR2/ULK1/mitophagy axis is a potential innovative therapeutic target for the prevention and management of bone loss.

01 Oct 2024·Cardiovascular Diagnosis and Therapy

Role of STK38L in atrial fibrillation-associated myocardial fibrosis: findings from RNA-seq analysis

Article

Author: Wang, Xiaochen ; Zhang, Yu ; Zhang, Ru ; Wang, Bangning ; Fang, Sihua

BackgroundMyocardial fibrosis is a key pathological feature of many cardiovascular diseases, leading to cardiac dysfunction. Transforming growth factor β1 (TGF-β1) induces the proliferation and activation of cardiac fibroblasts (CFs), key contributors to myocardial fibrosis. To explore the mechanism underlying myocardial fibrosis, we aimed to determine whether serine/threonine kinase 38 like (STK38L) contributes to the development of myocardial fibrosis by regulating the proliferation and activation of CFs triggered by TGF-β1.MethodsIn this study, atrial tissue samples from atrial fibrillation (AF) patients with features of myocardial fibrosis (a category of atrial cardiomyopathy) and sinus rhythm (SR) patients without myocardial fibrosis were collected for RNA sequencing (RNA-seq). The specific molecule STK38L was identified. Primary mouse CFs were activated with TGF-β1 and subsequently transfected with STK38L-small interfering RNA (siRNA). The effect of STK38L-siRNA on fibroblast activation and proliferation was assessed using scratch and Cell Counting Kit-8 (CCK-8) assays. Furthermore, a mouse model of myocardial fibrosis induced by continuous subcutaneous injection of isoprenaline (ISO) was established to assess STK38L expression levels. Molecular experiments confirmed the expression of STK38L in fibrotic atrial tissues, ventricular tissues of ISO mouse, and primary CFs of neonatal mice.ResultsWe identified 1,870 genes exhibiting differential expression in the RNA-seq data between the AF and SR groups. Masson's trichrome staining revealed increased fibrosis in the heart tissues of the AF group. Elevated levels of STK38L were observed in the atrial tissues of the AF group and in the TGF-β1-stimulated primary mouse CFs. In vitro, STK38L knockdown suppressed mouse CFs activation and proliferation. Additionally, in vivo experiments showed that elevated mRNA levels of STK38L, periostin (POSTN), and collagen type I alpha 1 chain (COL1A1) in ISO-treated mouse hearts correlated with greater myocardial fibrosis, suggesting that STK38L plays an important role in the development of fibrosis.ConclusionsThis study revealed a significant correlation between increased STK38L expression and AF characterized by atrial fibrosis as well as between STK38L expression and the TGF-β1-related induction of myocardial fibrosis. Additionally, STK38L knockdown was shown to suppress CFs activation and proliferation under TGF-β1 stimulation. These findings suggest an important role of STK38L in the development of fibrosis, and help screen for new strategies to treat this complex disease.

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STK38L

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