Annexins - insights from knockout mice.

Abstract:

:Annexins are a highly conserved protein family that bind to phospholipids in a calcium (Ca2+) - dependent manner. Studies with purified annexins, as well as overexpression and knockdown approaches identified multiple functions predominantly linked to their dynamic and reversible membrane binding behavior. However, most annexins are found at multiple locations and interact with numerous proteins. Furthermore, similar membrane binding characteristics, overlapping localizations and shared interaction partners have complicated identification of their precise functions. To gain insight into annexin function in vivo, mouse models deficient of annexin A1 (AnxA1), A2, A4, A5, A6 and A7 have been generated. Interestingly, with the exception of one study, all mice strains lacking one or even two annexins are viable and develop normally. This suggested redundancy within annexins, but examining these knockout (KO) strains under stress conditions revealed striking phenotypes, identifying underlying mechanisms specific for individual annexins, often supporting Ca2+ homeostasis and membrane transport as central for annexin biology. Conversely, mice lacking AnxA1 or A2 show extracellular functions relevant in health and disease that appear independent of membrane trafficking or Ca2+ signaling. This review will summarize the mechanistic insights gained from studies utilizing mouse models lacking members of the annexin family.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Grewal T,Wason SJ,Enrich C,Rentero C

doi

10.1515/hsz-2016-0168

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

1031-53

issue

10

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.just-accepted/hsz-2016-0168/hsz-2016-0168.

journal_volume

397

pub_type

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