High impact information on Dnm2

• Here we show that cortactin associates with the Golgi to regulate the actin- and Dyn2-dependent transport of cargo [1].
• These findings support the idea of an Arf1-activated recruitment of an actin, cortactin and Dyn2 complex that is essential for Golgi function [1].
• It binds directly to dynamin-2 (Dyn2), a large GTPase that mediates the formation of vesicles from the plasma membrane and the Golgi [1].
• Furthermore, selective disruption of the cortactin-Dyn2 interaction significantly reduces the levels of Dyn2 at the Golgi and blocks the transit of nascent proteins from the trans-Golgi network, resulting in swollen and distended cisternae [1].
• By Northern blot analysis and isoform-specific PCR, Dyn2 was found ubiquitously in adult rat tissues as two transcripts of 3.5 kb and 4 kb; the highest levels were found in testis [2].

Biological context of Dnm2

• In nonneural tissues, the dynamin-2 isoform participates in the formation of clathrin-coated vesicles during receptor endocytosis [3].
• Transient overexpression of these SH3 domains also reduced the localization of dynamin-2 to clathrin-coated pits [3].
• Thus, Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial transport of albumin [4].
• Intense expression of dynamin 2 during spermatogenesis suggests that this protein plays an important role in this process [5].

Anatomical context of Dnm2

• These data indicate that, similar to the recruitment of dynamin-1 during the recycling of synaptic vesicles, interaction of the dynamin-2 PRD with SH3 domains of proteins such as the amphiphysins and endophilins is essential for AT1A receptor endocytosis [3].
• In support of these distinctive physical interactions, we find that the different Dyn2 forms, when expressed as GTPase-defective mutants, exert markedly different inhibitory effects on caveolae internalization, as assayed by cholera toxin uptake [6].
• Immunoelectron microscopy of lung endothelium or a cultured hepatocyte cell line stained with antibodies for Dyn2 and Cav1 shows that these proteins co-localize to caveolae [6].
• Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells [4].
• Localization of dynamin 2 in rat seminiferous tubules during the spermatogenic cycle [5].

Associations of Dnm2 with chemical compounds

• Dynamin-2 molecules with mutant pleckstrin homology domains or deleted proline-rich domains (PRD) exerted dominant negative inhibition on the endocytosis of radiolabeled angiotensin II [3].
• In cells expressing a dominant-negative mutant of protein phosphatase 2A, dopamine failed to dephosphorylate dynamin-2 and to reduce Na(+),K(+)-ATPase activity [7].

Physical interactions of Dnm2

• Caveolin-1 interacts directly with dynamin-2 [6].
• In this study, the mechanism of dynamin-2 action was explored during endocytosis of the G protein-coupled AT1A angiotensin receptor expressed in Chinese hamster ovary cells [3].

Other interactions of Dnm2

• Expression of kinase-defective Src mutant interfered with the association between dynamin-2, which caveolin-1 and prevented the uptake of albumin [4].
• Dynamin 2, a dynamin isoform, is expressed most intensely in testicular tissue; however, precise localization has never been studied [5].
• However, the large GTPase dynamin 2 is implicated in the endocytosis of mGluR5 in COS-7. mGluR5 is the first shown member of the group C G-protein coupled receptor family internalized by a nonconventional pathway [8].
• Immunofluorescence labeling and freeze-fracture electron microscopy showed that dominant-negative dynamin 1 and dynamin 2 mutants prevent the release of clathrin-coated pits from the plasma membrane and induce an accumulation of AQP2 on the plasma membrane of AQP2-transfected cells [9].
• In the klotho deficient mouse testis, which demonstrates disorder in spermatogenesis, expression of dynamin 2 and dynamin 3 was drastically reduced indicating possible association of these proteins with spermatogenesis [10].

Analytical, diagnostic and therapeutic context of Dnm2

• Immunohistochemistrical examination and Western blot analysis were conducted using dynamin 2 specific antibody [5].
• By immunofluorescence it was revealed that dynamin 2 colocalizes with clathrin both at the plasmamembrane and at Golgi in a cell line of Sertoli cells [10].

References