Lysosomal targeting of autophagosomes by the TECPR domain of TECPR2

Fraiberg, Milana; Tamim-Yecheskel, Bat-Chen; Kokabi, Kamilya; Subic, Nemanja; Heimer, Gali; Eck, Franziska; Nalbach, Karsten; Behrends, Christian; Ben‐Zeev, Bruria; Shatz, Oren; Elazar, Zvulun

doi:10.1080/15548627.2020.1852727

Cited by 22 publications

(19 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TECPR2 is a binding partner of the mammalian Atg8 protein family and a possible positive regulator of autophagy [ 9 – 11 ]. Fraiberg et al [ 12 ] showed that the protein encoded by TECPR2 is involved in the targeting of autophagosomes to lysosomes; this process is impaired by mutations in the TECPR2 gene, resulting in autophagosomes that cannot be eliminated and for which the accumulation leads to neurodegenerative diseases. To improve understanding of TECPR2 gene function, Tamim-Yecheskel et al established a TECPR2 knockout mouse model.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Novel detection of mutation in the TECPR2 gene in a Chinese hereditary spastic paraplegia 49 patient: a case report

et al. 2022

View full text Add to dashboard Cite

Background Hereditary spastic paraplegia 49 (HSP49) is an autosomal recessive genetic disease first discovered in 2012; and which the mutation primarily affects Bukharian Jewish patients. Case presentation The present case reports the first instance of HSP49 detected in China. The patient had normal mental development and good athletic ability before 10 years old and presented with instable temperature, mental retardation, spastic ataxia, and paroxysmal convulsions. Genetic diagnosis was based on detection of whole exons and two heterozygous variants in the exon region of the TECPR2 gene: c.1729C > T and c.4189G > A. Mutations at these two sites have not been previously reported. Conclusions This case expands the gene mutation spectrum and clinical phenotypic characteristics of autosomal recessive HSP in China; moreover, it indicates differences in the clinical phenotype of HSP49 in different ethnicities. In addition, this reported provides further evidence regarding the effectiveness of targeted next-generation sequencing technology in improving the efficiency and diagnostic rate of genetic diagnosis of HSP.

show abstract

Section: Discussionmentioning

confidence: 99%

“…TECPR2 is a binding partner of the mammalian Atg8 protein family and a possible positive regulator of autophagy [9][10][11]. Fraiberg et al [12] showed that the protein encoded by TECPR2 is involved in the targeting of autophagosomes to lysosomes; this process is impaired by mutations in the Fig. 3 Brain EEG findings.…”

Section: Discussionmentioning

confidence: 99%

Novel detection of mutation in the TECPR2 gene in a Chinese hereditary spastic paraplegia 49 patient: a case report

et al. 2022

View full text Add to dashboard Cite

show abstract

“…TECPR2 regulates autophagy by maintaining functional endoplasmic exit sites, which serve as scaffolds for autophagosome formation [ 157 ]. However, recent studies also suggest a role for TECPR2 in the lysosomal targeting of autophagosomes [ 158 , 159 ].…”

Section: Autophagy and Neurodevelopmental Disordersmentioning

confidence: 99%

Towards a better understanding of the neuro-developmental role of autophagy in sickness and in health

Zapata‐Muñoz¹,

Villarejo‐Zori²,

Largo-Barrientos³

et al. 2021

CST

View full text Add to dashboard Cite

Autophagy is a critical cellular process by which biomolecules and cellular organelles are degraded in an orderly manner inside lysosomes. This process is particularly important in neurons: these post-mitotic cells cannot divide or be easily replaced and are therefore especially sensitive to the accumulation of toxic proteins and damaged organelles. Dysregulation of neuronal autophagy is well documented in a range of neurodegenerative diseases. However, growing evidence indicates that autophagy also critically contributes to neurodevelopmental cellular processes, including neurogenesis, maintenance of neural stem cell homeostasis, differentiation, metabolic reprogramming, and synaptic remodelling. These findings implicate autophagy in neurodevelopmental disorders. In this review we discuss the current understanding of the role of autophagy in neurodevelopment and neurodevelopmental disorders, as well as currently available tools and techniques that can be used to further investigate this association.

show abstract

“…This complex allows the Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated fusion between the outer membrane of the autophagosome and the lysosomal membrane. Notably, the syntaxin 17 (STX17) and synaptosomal-associated protein 29 (SNAP29) autophagosomal SNAREs and the lysosomal vesicle-associated membrane protein 8 (VAMP8) are involved in this process [ 60 , 116 , 137 ]. Mutations in three subunits of the HOPS complex, VPS11, VPS16 and VPS41, have been linked to neurological disorders.…”

Section: Autophagy Defects In Hspmentioning

confidence: 99%

“…A link between SPG49 mutations and autophagy has been made by the observation of a defect in autophagy in SPG49 patient-derived fibroblasts [ 152 ]. Recently, it has been proposed that TECPR2 regulates autophagosome–lysosome tethering and fusion by binding the autophagosome with its LC3-interacting region (LIR) and its interaction with HOPS [ 60 ]. The precise molecular function of TECPR2 in this model still has to be explored but it is consistent with the observation of autophagosome accumulation in the brain and spinal cord of the Tecpr2 −/− mouse model, suggesting an altered delivery of autophagosomes to lysosomes [ 61 ].…”

Section: Autophagy Defects In Hspmentioning

confidence: 99%

Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia

Marchesi

Leblanc

Stevanin

2021

Cells

View full text Add to dashboard Cite

Hereditary spastic paraplegia (HSP) refers to a group of neurological disorders involving the degeneration of motor neurons. Due to their clinical and genetic heterogeneity, finding common effective therapeutics is difficult. Therefore, a better understanding of the common pathological mechanisms is necessary. The role of several HSP genes/proteins is linked to the endolysosomal and autophagic pathways, suggesting a functional convergence. Furthermore, impairment of these pathways is particularly interesting since it has been linked to other neurodegenerative diseases, which would suggest that the nervous system is particularly sensitive to the disruption of the endolysosomal and autophagic systems. In this review, we will summarize the involvement of HSP proteins in the endolysosomal and autophagic pathways in order to clarify their functioning and decipher some of the pathological mechanisms leading to HSP.

show abstract

Lysosomal targeting of autophagosomes by the TECPR domain of TECPR2

Cited by 22 publications

References 31 publications

Novel detection of mutation in the TECPR2 gene in a Chinese hereditary spastic paraplegia 49 patient: a case report

Novel detection of mutation in the TECPR2 gene in a Chinese hereditary spastic paraplegia 49 patient: a case report

Towards a better understanding of the neuro-developmental role of autophagy in sickness and in health

Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia

Contact Info

Product

Resources

About