Dnajc13 Protein (Rme 8) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
**Protein Name:** DNAJC13 (RME-8)
**Gene:** DNAJC13
**UniProt ID:** Q7Z594
**Molecular Weight:** 206 kDa
**Subcellular Localization:** Endosomes, Cytoplasm
**Protein Family:** Hsp40 (DNAJ) family
**Aliases:** RME-8, Receptor-mediated endocytosis 8
DNAJC13 (also known as RME-8) is a J-domain containing protein that functions in endosomal trafficking. It plays important roles in protein sorting through the endosomal system and has been implicated in Parkinson's disease.
DNAJC13 contains:
- J-domain: N-terminal region for Hsp70 interaction
- WD40 repeats: Multiple WD40 repeat domains forming a beta-propeller
- Plant homeodomain (PHD): Zinc finger domain for protein interactions
DNAJC13/RME-8 is involved in endosomal trafficking:
- Endosomal Sorting: Regulates early endosome function and cargo recycling
- Clathrin Dynamics: Interacts with clathrin coat components
- Protein Sorting: Facilitates sorting of membrane proteins through endosomal compartments
- Autophagy: Modulates autophagosome formation and maturation
- Synaptic Vesicle Cycling: Contributes to endocytic recycling at synapses
DNAJC13 mutations cause autosomal dominant PD:
- The p.N855S mutation is pathogenic
- Alters endosomal sorting and protein clearance
- Contributes to alpha-synuclein aggregation
- Late-onset typical PD phenotype
¶ Lewy Body Dementia
DNAJC13 variants may modify DLB risk:
- Altered endosomal function in Lewy body formation
- Interaction with alpha-synuclein pathology
DNAJC13 has been implicated in essential tremor.
| Strategy |
Approach |
Status |
| Small Molecule Modulators |
Endosomal trafficking enhancers |
Research |
| Gene Therapy |
AAV-mediated DNAJC13 modulation |
Theoretical |
| Autophagy Enhancement |
mTOR inhibitors, TFEB activators |
Preclinical |
-
Vilarino-Guell C, et al. (2014). "DNAJC13 mutations in Parkinson disease." Am J Hum Genet 94(1):106-115. PMID:24444654.[1]
-
Fujiwara H, et al. (2016). "RME-8 functions in endosomal trafficking." J Cell Sci 129(Pt 6):1085-1095. PMID:27026525.[2]
-
Zhang J, et al. (2018). "DNAJC13 and endosomal dysfunction in PD." Neurobiol Dis 115:45-57. PMID:29486216.[3]
DNAJC13-related Parkinson's disease has distinct features:
- Typical Lewy body pathology
- Rapid disease progression in some families
- Good levodopa response initially
- May present with dementia in later stages
- Autosomal dominant inheritance
- p.N855S mutation identified in multiple families
- Variable penetrance suggesting modifier genes
- Possible gene-environment interactions
- Standard PD medications effective initially
- Dopamine agonists and levodopa
- Physical therapy and exercise
- Deep brain stimulation in select cases
- Understanding endosomal dysfunction in PD
- Developing Hsp70-based therapeutics
- Biomarker development for early detection
- Gene therapy approaches
- Knock-in mouse models with p.N855S
- Patient-derived neurons for drug screening
- Yeast models for protein aggregation
- Drosophila models for in vivo studies
DNAJC13 participates in protein networks:
| Partner |
Interaction |
Functional Consequence |
| Hsc70 (HSPA8) |
J-domain binding |
ATP-dependent protein remodeling |
| Clathrin |
Coat interaction |
Endosomal sorting |
| RAB proteins |
RAB5, RAB7 |
Endosome maturation |
| Auxilin (DNAJC6) |
Co-chaperone |
Synaptic vesicle endocytosis |
| GGA proteins |
Sorting |
Cargo trafficking |
| Strategy |
Approach |
Stage |
| Hsp70 Modulation |
2-phenylethynesulfonamide (PES) |
Preclinical |
| Endosomal Function |
RAB5 modulators |
Research |
| Gene Therapy |
AAV-DNAJC13 |
Conceptual |
| Small Molecule |
J-domain inhibitors |
Early discovery |
The study of Dnajc13 Protein (Rme 8) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Vallelonga F, et al. (2020). DNAJC13 mutations in Parkinson's disease. J Parkinsons Dis 10(3):1023-1034.
- Fujiwara H, et al. (2016). RME-8 function in endosomal trafficking. Mol Biol Cell 27(11):1793-1803.
- Shi M, et al. (2021). Endosomal dysfunction in neurodegenerative disease. Nat Rev Neurosci 22(8):485-498.
- Vilarino-Guell C, et al. (2014). DNAJC13 mutations in Parkinson disease. Am J Hum Genet 94(1):106-115. PMID:24444654.
- Fujiwara H, et al. (2016). RME-8 functions in endosomal trafficking. J Cell Sci 129(Pt 6):1085-1095. PMID:27026525.
- Zhang J, et al. (2018). DNAJC13 and endosomal dysfunction in PD. Neurobiol Dis 115:45-57. PMID:29486216.