Microtubule Retrograde Motors and Their Role in Retroviral Transport

Abstract

Following entry into the host cell, retroviruses generate a dsDNA copy of their genomes via reverse transcription, and this viral DNA is subsequently integrated into the chromosomal DNA of the host cell. Before integration can occur, however, retroviral DNA must be transported to the nucleus as part of a ‘preintegration complex’ (PIC). Transporting the PIC through the crowded environment of the cytoplasm is challenging, and retroviruses have evolved different mechanisms to accomplish this feat. Within a eukaryotic cell, microtubules act as the roads, while the microtubule-associated proteins dynein and kinesin are the vehicles that viruses exploit to achieve retrograde and anterograde trafficking. This review will examine the various mechanisms retroviruses have evolved in order to achieve retrograde trafficking, confirming that each retrovirus has its own strategy to functionally subvert microtubule associated proteins.

Microtubule stabilising peptides: new paradigm towards management of neuronal disorders

“…The clearing mechanism itself could be compromised by disease. [44][45][46] Different pathogenic factors can disrupt the mechanism for clearing of misfolded proteins, which can result in the misorientation of MTs. 47 Deterioration in MT mass is often connected to neurodegenerative diseases.…”

HIV Capsid and Integration Targeting

“…A number of cellular factors that participate in microtubule-dependent transport mechanisms have been shown to interact with HIV-1 CA (see [ 59 ] and [ 60 ] for recent reviews), including microtubule-associated proteins 1 (MAP1) [ 61 ], fasciculation and elongation factor zeta 1 (FEZ1) [ 62 , 63 ], diaphanous 2 (Dia2) [ 64 ], Bicaudal D2 (BICD2) [ 65 , 66 ], cytoplasmic linker-associated protein 2 (CLASP2) [ 67 ], and cytoplasmic linker protein 170 (CLIP170) [ 68 ]. Although these studies established contributions from these binding factors to HIV-1 retrograde movement within cells, it is unclear if infection would require the viral core to bind to all of these proteins simultaneously.…”

Long-range electrostatic interactions significantly modulate the affinity of dynein for microtubules

“…Cytoplasmic dynein (hereafter called dynein unless otherwise specified) is a microtubule minus-end-directed motor protein that drives diverse functions in eukaryotic cells, including retrograde intracellular transport ( 1 ), mitotic spindle assembly ( 2 ), chromosome segregation ( 3 ), nucleus positioning ( 4 , 5 ), and cytoskeletal network organization ( 6 ). Dynein dysfunction is associated with several diseases; in particular, neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s disease ( 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ). Cytoplasmic dynein is a 1.4 MDa protein complex with two copies of a 530 kDa heavy chain and associated regulatory light, intermediate light, and intermediate chains ( 16 ).…”