Azzurra De Luca's research while affiliated with Università del Salento and other places
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Publications (4)
Rab7b is a recently identified member of the Rab GTPase protein family and has high similarity to Rab7. It has been reported that Rab7b is lysosome associated, that it is involved in monocytic differentiation and that it promotes lysosomal degradation of TLR4 and TLR9. Here we investigated further the localization and function of this GTPase. We fo...
Four missense mutations, that target highly conserved amino acid residues in the small GTPase Rab7, have been associated with the Charcot-Marie-Tooth (CMT) type 2B phenotype. CMT2B peripheral axonal neuropathies are characterized by severe sensory loss, often complicated by infections, arthropathy, and amputations. Here, we have investigated the bi...
Charcot-Marie-Tooth (CMT) type 2 neuropathies are a group of autosomal-dominant axonal disorders genetically and clinically heterogeneous. In particular, CMT type 2B (CMT2B) neuropathies are characterized by severe sensory loss, often complicated by infections, arthropathy, and amputations. Recently, four missense mutations in the small GTPase Rab7...
The Rab-interacting lysosomal protein (RILP) has been identified as an effector for the small GTPases Rab7 and Rab34. It has been demonstrated that Rab7 and RILP are key proteins for the biogenesis of lysosomes and phagolysosomes. Indeed, expression of dominant negative mutants of Rab7 or of the C-terminal half of RILP impairs biogenesis and functi...
Citations
... It can also regulate the transport of transferrin (iron) receptors, the uptake of antigens (such as viruses and spirochetes), and the formation of T-cell complexes to affect antigen presentation [18,19,24]. As the principal regulators of intracellular membrane trafficking, Rab proteins are required at the different steps of antigen processing, presentation, and loading onto MHC class I molecules, including in the maturation of early endosomes (Rab5a) and late endosomes (Rab7) [25]. Rab7b is required for normal lysosome function and in particular, it is an essential factor for the retrograde transport of molecules from endosomes to the trans-Golgi network (TGN) [26]. ...
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... It associates with the multi-subunit complex dynactin and promotes the lysosomal transport towards the microtubule minus-ends. Many different factors, including small GTPases, adaptor proteins, phosphoinositides and cation channels, modulate dynein-dependent centripetal transport of endolysosomes in a different fashion (figure 1c-f ) [63][64][65][66][67][68][69][70][71][72][73]. Emerging evidence has demonstrated how the centripetal localization of the endolysosomal compartment is controlled by septins (SEPTs) [74,75], a family of GTP-binding proteins, which multimerize into higher order oligomers and polymers that associate with cell membranes and cytoskeleton [76]. ...
... The roles of Rab GTPases in neurodegeneration can be either direct or indirect. For example, direct effects can be seen in neurodegeneration caused by mutations in rab genes and/or in the genes that encode Rab-associated proteins (Spinosa et al., 2008;Lesage et al., 2015), while alterations in Rab-dependent trafficking are associated with disease progression indirectly (Ginsberg et al., 2011;Lai et al., 2015). ...
... Although the biochemical and functional properties of the CMT2B-causing RAB7 mutant proteins have been previously investigated [54][55][56][57][58] , the exact mechanism by which mutated RAB7, albeit ubiquitous, causes dysfunction in peripheral neurons is still not clear. Emerging evidence has suggested a key role of the crosstalk between mitochondria and lysosomes in cellular physiology and its dysregulation in neurodegenerative disease as mitochondrial impairment can influence lysosomal function and vice versa 59 . ...
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