DNM1L

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Dynamin 1-like
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DNM1L ; DLP1; DRP1; DVLP; DYMPLE; EMPF; HDYNIV
External IDs OMIM603850 MGI1921256 HomoloGene6384 GeneCards: DNM1L Gene
EC number 3.6.5.5
RNA expression pattern
PBB GE DNM1L 203105 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10059 74006
Ensembl ENSG00000087470 ENSMUSG00000022789
UniProt O00429 Q8K1M6
RefSeq (mRNA) NM_001278463 NM_001025947
RefSeq (protein) NP_001265392 NP_001021118
Location (UCSC) Chr 12:
32.83 – 32.9 Mb
Chr 16:
16.31 – 16.36 Mb
PubMed search [1] [2]

Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the DNM1L gene.[1][2][3]

Structure[edit]

Drp1, which is a member of the dynamin superfamily of proteins, consists of a GTPase and GTPase effector domain that are separated from each other by a helical segment of amino acids.[4] There are 3 mouse and 6 human isoforms of Drp1, including a brain-specific variant.[5]

Function[edit]

Mitochondria are constantly fusing and dividing with each other, forming large, reticular networks. In humans, mitochondrial fission is regulated by Fis1 and Drp1. Several studies have indicated that Drp1 is essential for proper embryonic development. Drp1 knockout mice exhibit abnormal brain development and die around embryonic day 12. In neural specific Drp1 knockout mice, brain size is reduced and apoptosis is increased. Synapse formation and neurite growth are also impaired. A second group of researchers generated another neural specific knockout mouse line. They found that knocking out Drp1 resulted in the appearance of large mitochondria in Purkinje cells and prevented neural tube formation.[5]

In humans, loss of Drp1 function affects brain development and is also associated with early mortality.[4]

Interactions[edit]

The majority of knowledge about mitochondrial fission comes from studies with yeast. The yeast homolog of Drp1 is dynamin-1 (Dnm1), which interacts with Fis1 through Mdv1. This interaction causes Dnm1 to oligomerize and form rings around dividing mitochondria at the so-called "constriction point".[4] Drp1 has also been shown to interact with GSK3B.[2]

Post-translational modifications to Drp1 (e.g. phosphorylation) can alter its activity and affect the rate of fission.[6]

References[edit]

  1. ^ Shin HW, Shinotsuka C, Torii S, Murakami K, Nakayama K (Feb 1998). "Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p". J Biochem 122 (3): 525–30. doi:10.1093/oxfordjournals.jbchem.a021784. PMID 9348079. 
  2. ^ a b Hong YR, Chen CH, Cheng DS, Howng SL, Chow CC (Oct 1998). "Human dynamin-like protein interacts with the glycogen synthase kinase 3beta". Biochem Biophys Res Commun 249 (3): 697–703. doi:10.1006/bbrc.1998.9253. PMID 9731200. 
  3. ^ "Entrez Gene: DNM1L dynamin 1-like". 
  4. ^ a b c Westermann B (December 2010). "Mitochondrial fusion and fission in cell life and death". Nat Rev Mol Cell Biol 11 (12): 872–884. doi:10.1038/nrm3013. PMID 21102612. 
  5. ^ a b Reddy PH, Reddy TP, Manczak M, Calkins MJ, Shirindeb U, Mao P (June 2011). "Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases". Brain Res Rev 67 (1-2): 103–118. doi:10.1016/j.brainresrev.2010.11.004. PMID 21145355. 
  6. ^ Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E (July 2008). "Mitochondrial fragmentation in neurodegeneration". Nat Rev Neurosci 9 (7): 505–518. doi:10.1038/nrn2417. PMID 18568013. 

Further reading[edit]

External links[edit]