Growth factors in wound healing: the present and the future?

Numerous clinical studies have confirmed the pivotal role growth factors play in wound healing and their diminished levels in the chronic wound. Despite promising early studies treating chronic wounds with growth factors, results with traditional bolus dosing of a single growth factor have yielded insignificant results. Disappointing results have been theorized to be the result of growth factors inherent short half-life, a hostile microenvironment rich in protease activity, and poor delivery mechanisms failing to deliver effective dosages in an appropriate temporal manner.

Truncated isoforms of Kap60 facilitate trafficking of Heh2 to the nuclear envelope.

Isoforms of importin-α have been identified in insect and human cells, and cross-linking experiments suggest that at least one isoform in each species participates in the targeting of integral membrane proteins to the inner nuclear membrane (INM). To directly test this hypothesis, an assay was developed using Saccharomyces cerevisiae. The data show that internal promoters are present within KAP60, and the nested transcripts are translated into three isoforms: Kap60-44, Kap60-30 and Kap60-10.

Baculovirus data suggest a common but multifaceted pathway for sorting proteins to the inner nuclear membrane.

Multiple unique protein markers sorted to the inner nuclear membrane (INM) from the Autographa californica nucleopolyhedrovirus occlusion-derived virus (ODV) envelope were used to decipher common elements of the sorting pathway of integral membrane proteins from their site of insertion into the membrane of the endoplasmic reticulum (ER) through their transit to the INM. The data show that during viral infection, the viral protein FP25K is a partner for all known ODV envelope proteins and that BV/ODV-E26 (designated E26) is a partner for some, but not all, such proteins. The association with the ER membrane of FP25K, E26, and the cellular INM-sorting protein importin-alpha-16 is not static; rather, these sorting proteins are actively recruited to the ER membrane based upon requirements of the proteins in transit to the INM.

Molecular biology of the baculovirus occlusion-derived virus envelope.

Study of the biology of the occlusion-derived virus (ODV) of the baculovirus Autographa californica nucleopolyhedrovirus provides opportunities to reveal new discoveries into the mechanism of several cellular pathways. The synchronous pulse of multiple ODV envelope proteins that integrate into the endoplasmic reticulum (ER) and traffic to the nuclear membranes on their way to the ODV envelope provide a unique tool to study the mechanisms of integral membrane protein trafficking from the ER to the outer and inner nuclear membrane. Studies of the formation of virus-induced, intranuclear membrane microvesicles provide insight on mechanisms that alter fluidity and regulate budding of the inner nuclear membrane.

Early sorting of inner nuclear membrane proteins is conserved.

Spodoptera frugiperda (Sf9) importin-alpha-16 is a translocon-associated protein that participates in the early sorting pathway of baculovirus integral membrane proteins destined for the inner nuclear membrane (INM). To discern whether sorting intermediate protein complexes like those observed in insect cells are also formed with mammalian INM proteins, cross-linked complexes of importin-alpha-16 with human lamin B receptor (LBR) and nurim were examined. Both LBR and nurim cross-link with Sf9 importin-alpha-16 during cotranslational membrane integration and remain proximal with importin-alpha-16 after integration into the endoplasmic reticulum membrane and release from the translocon.