The XLMR gene ACSL4 plays a role in dendritic spine architecture.
ACSL4 is a gene involved in non-syndromic X-linked mental retardation. It encodes for a ubiquitous protein that adds coenzyme A to long-chain fatty acids, with a high substrate preference for arachidonic acid. It presents also a brain-specific isoform deriving from an alternative splicing and containing 41 additional N-terminal amino acids. To start to unravelling the link between ACSL4 and mental retardation, we have performed molecular and cell biological studies. By retro-transcription polymerase chain reaction analyses we identified a new transcript with a shorter 5'-UTR region. By immunofluorescence microscopy in embryonic rat hippocampal neurons we report that ACSL4 is associated preferentially to endoplasmic reticulum tubules. ACSL4 knockdown by siRNAs in hippocampal neurons indicated that this protein is largely dispensable for these cells' gross architectural features (i.e. axonal and dendritic formation and final length) yet it is required for the presence of normal spines. In fact, reduced levels of ACSL4 led to a significant reduction in dendritic spine density and an alteration in spine/filopodia distribution. The possible mechanisms behind this phenotype are discussed.
Meloni
I
I
Medical Genetics Unit, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy.
Parri
V
V
De Filippis
R
R
Ariani
F
F
Artuso
R
R
Bruttini
M
M
Katzaki
E
E
Longo
I
I
Mari
F
F
Bellan
C
C
Dotti
C G
CG
Renieri
A
A
D000199:Actins / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D037282:Calreticulin / Q000378:metabolism; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000235:genetics* / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014162:Transfection / Q000379:methods; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D000199:Actins; D037282:Calreticulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase